{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:32Z","timestamp":1787027852106,"version":"build-2736575974"},"reference-count":178,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Comprehensive Cancer Center Niedersachsen (CCC-N)","award":["ZN3440"],"award-info":[{"award-number":["ZN3440"]}]},{"name":"Bruno and Helene J\u00f6ster Foundation","award":["ZN3440"],"award-info":[{"award-number":["ZN3440"]}]},{"name":"German Research Foundation (DFG)","award":["ZN3440"],"award-info":[{"award-number":["ZN3440"]}]},{"name":"Federal Ministry of Education and Research (BMBF)","award":["ZN3440"],"award-info":[{"award-number":["ZN3440"]}]},{"name":"REBIRTH Center for Translational Regenerative Medicine","award":["ZN3440"],"award-info":[{"award-number":["ZN3440"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cervical cancer is one of the most common malignancies in women, and the majority of cases are caused by infection with high-risk human papilloma virus (HPV) subtypes. Despite effective preventative measures, such as vaccinations against HPV, over 300,000 women die world-wide from cervical cancer each year. Once cervical cancer is diagnosed, treatment may consist of radial hysterectomy, or chemotherapy and radiotherapy, or a combination of therapies dependent upon the disease stage. Unfortunately, overall prognosis for patients with metastatic or recurrent disease remains poor. In these cases, immunotherapies may be useful based on promising preclinical work, some of which has been successfully translated to the clinic. For example, approaches using monoclonal antibodies directed against surface proteins important for control of immune checkpoints (i.e., immune checkpoint inhibitors) were shown to improve outcome in many cancer settings, including cervical cancer. Additionally, initial clinical studies showed that application of cytotoxic immune cells modified to express chimeric antigen receptors (CAR) or T cell receptors (TCR) for better recognition and elimination of tumor cells may be useful to control cervical cancer. This review explores these important topics, including strengths and limitations of standard and developing approaches, and how some novel treatment strategies may be optimally used to offer the best possible treatment for cervical cancer patients.<\/jats:p>","DOI":"10.3390\/cancers15010263","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T03:00:59Z","timestamp":1672628459000},"page":"263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Towards Novel Gene and Cell Therapy Approaches for Cervical Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Robert","family":"Polten","sequence":"first","affiliation":[{"name":"Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Kutle","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4542-5833","authenticated-orcid":false,"given":"Jens","family":"Hachenberg","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Department of Obstetrics and Gynecology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0117-4366","authenticated-orcid":false,"given":"R\u00fcdiger","family":"Klapdor","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Department of Obstetrics and Gynecology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Morgan","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Schambach","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Division of Hematology\/Oncology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA","volume":"71","author":"Sung","year":"2021","journal-title":"Cancer J. Clin."},{"key":"ref_2","unstructured":"(2022, December 29). The American Cancer Society Cancer.org. 1.800.227.2345. Available online: https:\/\/www.cancer.org\/content\/dam\/CRC\/PDF\/Public\/8893.00.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Gasparini, R., and Panatto, D. (2009). Cervical cancer: From Hippocrates through Rigoni-Stern to zur Hausen. Vaccine, 27.","DOI":"10.1016\/j.vaccine.2008.11.069"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1002\/cncr.25553","article-title":"A note from history: Landmarks in history of cancer, part 1","volume":"117","author":"Hajdu","year":"2011","journal-title":"Cancer"},{"key":"ref_5","first-page":"169","article-title":"The extended abdominal operation for carcinoma uteri (based on 500 operative cases)","volume":"66","author":"Wertheim","year":"1912","journal-title":"Am. J. Obstet. Dis. Women Child."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Giannini, A., Bogani, G., Vizza, E., Chiantera, V., Lagan\u00e0, A.S., Muzii, L., Salerno, M.G., Caserta, D., and D\u2019Oria, O. (2022). Advances on Prevention and Screening of Gynecologic Tumors: Are We Stepping Forward?. Healthcare, 10.","DOI":"10.3390\/healthcare10091605"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ygyno.2019.04.004","article-title":"Pathway to the Papanicolaou smear: The development of cervical cytology in twentieth-century America and implications in the present day","volume":"154","author":"Swailes","year":"2019","journal-title":"Gynecol. Oncol."},{"key":"ref_8","first-page":"CD010260","article-title":"Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer","volume":"7","author":"Kokka","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.vaccine.2012.07.055","article-title":"Global burden of human papillomavirus and related diseases","volume":"30","author":"Forman","year":"2012","journal-title":"Vaccine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/nm1598","article-title":"Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan","volume":"13","author":"Roberts","year":"2007","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/nar\/gkw879","article-title":"The Papillomavirus Episteme: A major update to the papillomavirus sequence database","volume":"45","author":"Li","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.virol.2018.04.003","article-title":"Towards quality and order in human papillomavirus research","volume":"519","author":"Eklund","year":"2018","journal-title":"Virology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1002\/ijc.2910250509","article-title":"Zur Partial characterization of viral DNA from human genital warts (condylomata acuminata)","volume":"25","author":"Gissmann","year":"1980","journal-title":"Int. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.semcancer.2013.11.002","article-title":"The human papillomavirus family and its role in carcinogenesis","volume":"26","author":"Tommasino","year":"2014","journal-title":"Semin. Cancer Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/S1470-2045(10)70230-8","article-title":"Human papillomavirus genotype attribution in invasive cervical cancer: A retrospective cross-sectional worldwide study","volume":"11","author":"Quint","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/ijc.30716","article-title":"Worldwide burden of cancer attributable to HPV by site, country and HPV type","volume":"141","author":"Plummer","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/rmv.488","article-title":"Human papillomaviruses: Basic mechanisms of pathogenesis and oncogenicity","volume":"16","author":"Hebner","year":"2006","journal-title":"Rev. Med. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S1470-2045(08)70103-7","article-title":"Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: A retrospective cohort study","volume":"9","author":"McCredie","year":"2008","journal-title":"Lancet Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12180","DOI":"10.1073\/pnas.89.24.12180","article-title":"Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic","volume":"89","author":"Kirnbauer","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1097\/01.inf.0000253970.29190.5a","article-title":"Safety and persistent immunogenicity of a quadrivalent human papillomavirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents: A randomized controlled trial","volume":"26","author":"Reisinger","year":"2007","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.4161\/hv.7.12.18322","article-title":"Immunogenicity and safety of the HPV-16\/18 AS04-adjuvanted vaccine administered as a 2-dose schedule compared with the licensed 3-dose schedule: Results from a randomized study","volume":"7","author":"Romanowski","year":"2011","journal-title":"Hum. Vaccin."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1016\/j.vaccine.2021.01.074","article-title":"Immunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27\u201345 years of age compared to women 16\u201326 years of age: An open-label phase 3 study","volume":"39","author":"Joura","year":"2021","journal-title":"Vaccine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5753","DOI":"10.1016\/j.vaccine.2017.05.069","article-title":"Human papillomavirus vaccines: WHO position paper, May 2017\u2013Recommendations","volume":"35","year":"2017","journal-title":"Vaccine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1093\/jnci\/djp534","article-title":"Impact of Human Papillomavirus (HPV)-6\/11\/16\/18 Vaccine on All HPV-Associated Genital Diseases in Young Women","volume":"102","author":"Munoz","year":"2010","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S1473-3099(10)70225-5","article-title":"Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: Analysis of national sentinel surveillance data","volume":"11","author":"Donovan","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ali, H., Guy, R.J., Wand, H., Read, T.R.H., Regan, D.G., Grulich, A.E., Fairley, C.K., and Donovan, B. (2013). Decline in in-patient treatments of genital warts among young Australians following the national HPV vaccination program. BMC Infect. Dis., 13.","DOI":"10.1186\/1471-2334-13-140"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1056\/NEJMoa1917338","article-title":"HPV Vaccination and the Risk of Invasive Cervical Cancer","volume":"383","author":"Lei","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100836","DOI":"10.1016\/j.eclinm.2021.100836","article-title":"Human papillomavirus vaccination uptake in low-and middle-income countries: A meta-analysis","volume":"34","author":"Dorji","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1158\/1055-9965.EPI-16-0858","article-title":"Global cancer in women: Burden and trends","volume":"26","author":"Torre","year":"2017","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"167","DOI":"10.2147\/ITT.S273327","article-title":"Therapeutic Vaccines for HPV-Associated Malignancies","volume":"9","author":"Rumfield","year":"2020","journal-title":"ImmunoTargets Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41577-020-0306-5","article-title":"A guide to cancer immunotherapy: From T cell basic science to clinical practice","volume":"20","author":"Waldman","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12964-022-00854-y","article-title":"Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons","volume":"20","author":"Naimi","year":"2022","journal-title":"Cell Commun. Signal."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Qin, S., Xu, L., Yi, M., Yu, S., Wu, K., and Luo, S. (2019). Novel immune checkpoint targets: Moving beyond PD-1 and CTLA-4. Mol. Cancer, 18.","DOI":"10.1186\/s12943-019-1091-2"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/bs.apha.2021.01.002","article-title":"Review of immune checkpoint inhibitors in immuno-oncology","volume":"91","author":"Jacob","year":"2021","journal-title":"Adv. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1038\/modpathol.2015.108","article-title":"Enhanced expression of PD L1 in cervical intraepithelial neoplasia and cervical cancers","volume":"28","author":"Mezache","year":"2015","journal-title":"Mod. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/modpathol.2016.64","article-title":"Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix","volume":"29","author":"Heeren","year":"2016","journal-title":"Mod. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.7150\/jca.22532","article-title":"PD-L1 expression correlates with tumor infiltrating lymphocytes and response to neoadjuvant chemotherapy in cervical cancer","volume":"9","author":"Meng","year":"2018","journal-title":"J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S1470-2045(18)30859-3","article-title":"Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): A first-in-human, multicentre, phase 1\u20132 trial","volume":"20","author":"Concin","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1200\/JCO.18.01265","article-title":"Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: Results from the phase II KEYNOTE-158 study","volume":"37","author":"Chung","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/S0090-8258(21)00696-X","article-title":"Pembrolizumab treatment of advanced cervical cancer: Updated results from the phase II KEYNOTE-158 study","volume":"162","author":"Chung","year":"2021","journal-title":"Gynecol. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1056\/NEJMoa2112435","article-title":"Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer","volume":"385","author":"Colombo","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1056\/NEJMoa2112187","article-title":"Survival with Cemiplimab in Recurrent Cervical Cancer","volume":"386","author":"Tewari","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s40265-019-01249-z","article-title":"Novel Therapeutics for Recurrent Cervical Cancer: Moving Towards Personalized Therapy","volume":"80","author":"Cohen","year":"2020","journal-title":"Drugs"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kagabu, M., Nagasawa, T., Sato, C., Fukagawa, Y., Kawamura, H., Tomabechi, H., Takemoto, S., Shoji, T., and Baba, T. (2020). Immunotherapy for uterine cervical cancer using checkpoint inhibitors: Future directions. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072335"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.it.2022.11.002","article-title":"The heightened importance of the microbiome in cancer immunotherapy","volume":"44","author":"Villemin","year":"2022","journal-title":"Trends Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s13073-021-00923-w","article-title":"Role of the intestinal microbiome and microbial-derived metabolites in immune checkpoint blockade immunotherapy of cancer","volume":"13","author":"Hayase","year":"2021","journal-title":"Genome Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1126\/science.aac4255","article-title":"Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy","volume":"350","author":"Sivan","year":"2015","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"949490","DOI":"10.3389\/fimmu.2022.949490","article-title":"Antitumor effects of fecal microbiota transplantation: Implications for microbiome modulation in cancer treatment","volume":"13","author":"Xu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1748-717X-5-31","article-title":"Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients","volume":"5","author":"Chitapanarux","year":"2010","journal-title":"Radiat. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41572-020-0160-6","article-title":"Immune-related adverse events of checkpoint inhibitors","volume":"6","author":"Brahmer","year":"2020","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/acg2.84","article-title":"TRUCKS, the fourth-generation CAR T cells: Current developments and clinical translation","volume":"3","author":"Chmielewski","year":"2020","journal-title":"Adv. Cell Gene Ther."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Huynh, D., Winter, P., M\u00e4rkl, F., Endres, S., and Kobold, S. (2022). Beyond direct killing\u2014Novel cellular immunotherapeutic strategies to reshape the tumor microenvironment. Semin. Immunopathol., online ahead of print.","DOI":"10.1007\/s00281-022-00962-4"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.3389\/fimmu.2019.02250","article-title":"Engineered T Cell Therapy for Cancer in the Clinic","volume":"10","author":"Zhao","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41568-022-00491-0","article-title":"Natural killer cells in antitumour adoptive cell immunotherapy","volume":"22","author":"Laskowski","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1056\/NEJMoa1001294","article-title":"Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer","volume":"363","author":"Kantoff","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma","volume":"377","author":"Neelapu","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1056\/NEJMoa1709866","article-title":"Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia","volume":"378","author":"Maude","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"779356","DOI":"10.3389\/fonc.2022.779356","article-title":"Transcriptome Analysis Reveals the Immune Infiltration Profiles in Cervical Cancer and Identifies KRT23 as an Immunotherapeutic Target","volume":"12","author":"Li","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1056\/NEJMp048021","article-title":"Paul Ehrlich\u2019s Magic Bullets","volume":"350","author":"Schwartz","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0140-6736(00)04046-0","article-title":"Inflammation and cancer: Back to Virchow?","volume":"357","author":"Balkwill","year":"2001","journal-title":"Lancet"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1053\/j.gastro.2013.03.044","article-title":"Risk of colorectal high-grade dysplasia and cancer in a prospective observational cohort of patients with inflammatory bowel disease","volume":"145","author":"Beaugerie","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature01322","article-title":"Inflammation and Cancer","volume":"420","author":"Coussens","year":"2002","journal-title":"Nature"},{"key":"ref_63","first-page":"3333","article-title":"Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: A cancer-prone chronic inflammatory disease","volume":"60","author":"Hussain","year":"2000","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"181987","DOI":"10.1155\/2012\/181987","article-title":"Bladder cancer immunotherapy: BCG and beyond","volume":"2012","author":"Askeland","year":"2012","journal-title":"Adv. Urol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1146\/annurev.immunol.25.022106.141606","article-title":"Immunobiology of allogeneic hematopoietic stem cell transplantation","volume":"25","author":"Welniak","year":"2007","journal-title":"Annu. Rev. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"806","DOI":"10.7326\/0003-4819-108-6-806","article-title":"Bone marrow transplantation for chronic myelogenous leukemia in chronic phase. Increased risk for relapse associated with T-cell depletion","volume":"108","author":"Goldman","year":"1988","journal-title":"Ann. Intern. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/(SICI)1097-0142(19960401)77:7<1303::AID-CNCR12>3.0.CO;2-5","article-title":"Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma","volume":"77","author":"Clemente","year":"1996","journal-title":"Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.1200\/JCO.2007.15.0284","article-title":"Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures","volume":"26","author":"Antoine","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nrc3245","article-title":"The immune contexture in human tumours: Impact on clinical outcome","volume":"12","author":"Fridman","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/nri3789","article-title":"Immune cell promotion of metastasis","volume":"15","author":"Kitamura","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1111\/j.1349-7006.2006.00231.x","article-title":"Favorable prognosis of renal cell carcinoma with increased expression of chemokines associated with a Th1-type immune response","volume":"97","author":"Kondo","year":"2006","journal-title":"Cancer Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1093\/intimm\/dxl092","article-title":"Tumor cell expression of HLA-DM associates with a Th1 profile and predicts improved survival in breast carcinoma patients","volume":"18","author":"Oldford","year":"2006","journal-title":"Int. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1158\/0008-5472.CAN-10-2907","article-title":"Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, Th2, Treg, Th17) in patients with colorectal cancer","volume":"71","author":"Tosolini","year":"2011","journal-title":"Cancer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/jso.21725","article-title":"Evaluations of interferon-\u03b3\/interleukin-4 ratio and neutrophil\/lymphocyte ratio as prognostic indicators in gastric cancer patients","volume":"102","author":"Ubukata","year":"2010","journal-title":"J. Surg. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1016\/0959-8049(94)E0159-2","article-title":"Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma","volume":"30A","author":"Vesalainen","year":"1994","journal-title":"Eur. J. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1189\/jlb.0805455","article-title":"Multiple populations of T lymphocytes are distinguished by the level of CD4 and CD8 coexpression and require individual consideration","volume":"79","author":"Zloza","year":"2006","journal-title":"J. Leukoc. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/00313029600169274","article-title":"Infiltration by immunocompetent cells in early stage invasive carcinoma of the uterine cervix: A prognostic study","volume":"28","author":"Bethwaite","year":"1996","journal-title":"Pathology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1158\/0008-5472.CAN-06-3388","article-title":"High number of intraepithelial CD8+ tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancer","volume":"67","author":"Piersma","year":"2007","journal-title":"Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ygyno.2020.07.106","article-title":"Tumor-infiltrating lymphocytes predict survival outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy","volume":"159","author":"Ohno","year":"2020","journal-title":"Gynecol. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1084\/jem.20052494","article-title":"Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy","volume":"203","author":"Reits","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1084\/jem.20011983","article-title":"Pivotal role of dendritic cell-derived CXCL10 in the retention of T helper cell 1 lymphocytes in secondary lymph nodes","volume":"195","author":"Yoneyama","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.it.2016.09.006","article-title":"Dendritic Cells and Cancer Immunity","volume":"37","author":"Gardner","year":"2016","journal-title":"Trends Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Abakushina, E.V., Popova, L.I., Zamyatnin, A.A., Werner, J., Mikhailovsky, N.V., and Bazhin, A.V. (2021). The advantages and challenges of anticancer dendritic cell vaccines and nk cells in adoptive cell immunotherapy. Vaccines, 9.","DOI":"10.3390\/vaccines9111363"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.2174\/138161205774414565","article-title":"Therapeutic Vaccines for Cervical Cancer: Dendritic Cell-Based Immunotherapy","volume":"11","author":"Santin","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e1147641","DOI":"10.1080\/2162402X.2016.1147641","article-title":"A novel dendritic cell targeting HPV16 E7 synthetic vaccine in combination with PD-L1 blockade elicits therapeutic antitumor immunity in mice","volume":"5","author":"Liu","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3389\/fmed.2020.583708","article-title":"Immunotherapy Targeting Tumor-Associated Macrophages","volume":"7","author":"Liu","year":"2020","journal-title":"Front. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1590\/S1807-59322011001100006","article-title":"M2-Polarized tumor-associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma","volume":"66","author":"Zhang","year":"2011","journal-title":"Clinics"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Wang, H., Yung, M.M.H., Ngan, H.Y.S., Chan, K.K.L., and Chan, D.W. (2021). The impact of the tumor microenvironment on macrophage polarization in cancer metastatic progression. Int. J. Mol. Sci.","DOI":"10.3390\/ijms22126560"},{"key":"ref_89","first-page":"6842963","article-title":"Research Progress on Tumor-Associated Macrophages and Inflammation in Cervical Cancer","volume":"2020","author":"Liu","year":"2020","journal-title":"Biomed Res. Int."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Cendrowicz, E., Sas, Z., Bremer, E., and Rygiel, T.P. (2021). The role of macrophages in cancer development and therapy. Cancers, 13.","DOI":"10.3390\/cancers13081946"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.4049\/jimmunol.1100889","article-title":"M2 Macrophages Induced by Prostaglandin E 2 and IL-6 from Cervical Carcinoma Are Switched to Activated M1 Macrophages by CD4 + Th1 Cells","volume":"187","author":"Heusinkveld","year":"2011","journal-title":"J. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Anfray, C., Ummarino, A., And\u00f3n, F.T., and Allavena, P. (2020). Current strategies to target tumor-associated-macrophages to improve anti-tumor immune responses. Cells, 9.","DOI":"10.3390\/cells9010046"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Ren, J., Li, L., Yu, B., Xu, E., Sun, N., Li, X., Xing, Z., Han, X., Cui, Y., and Wang, X. (2022). Extracellular vesicles mediated proinflammatory macrophage phenotype induced by radiotherapy in cervical cancer. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-09194-z"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jitc-2020-001356","article-title":"Genetically engineered macrophages persist in solid tumors and locally deliver therapeutic proteins to activate immune responses","volume":"8","author":"Brempelis","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/eji.1830050208","article-title":"\u201cNatural\u201d killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype","volume":"5","author":"Kiessling","year":"1975","journal-title":"Eur. J. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.smim.2017.08.002","article-title":"Natural killer cell-mediated immunosurveillance of human cancer","volume":"31","author":"Malmberg","year":"2017","journal-title":"Semin. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/imm.13114","article-title":"Cancer immune escape: MHC expression in primary tumours versus metastases","volume":"158","author":"Garrido","year":"2019","journal-title":"Immunology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1097\/PAS.0000000000001506","article-title":"Loss of MHC class i expression in HPV-associated cervical and vulvar neoplasia: A potential mechanism of resistance to checkpoint inhibition","volume":"44","author":"Dibbern","year":"2020","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.immuni.2008.02.016","article-title":"NKG2D-Deficient Mice Are Defective in Tumor Surveillance in Models of Spontaneous Malignancy","volume":"28","author":"Guerra","year":"2008","journal-title":"Immunity"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/S0140-6736(00)03231-1","article-title":"Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: An 11-year follow-up study of a general population","volume":"356","author":"Imai","year":"2000","journal-title":"Lancet"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ccell.2017.06.009","article-title":"Control of Metastasis by NK Cells","volume":"32","author":"Gonzalez","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/ni1581","article-title":"Up on the tightrope: Natural killer cell activation and inhibition","volume":"9","author":"Lanier","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.it.2009.01.006","article-title":"NK cell education: Not an on-off switch but a tunable rheostat","volume":"30","author":"Brodin","year":"2009","journal-title":"Trends Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S0962-8924(97)01167-7","article-title":"Regulation through inhibitory receptors: Lessons from natural killer cells","volume":"7","author":"Burshtyn","year":"1997","journal-title":"Trends Cell Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1084\/jem.20100570","article-title":"Mature natural killer cells reset their responsiveness when exposed to an altered MHC environment","volume":"207","author":"Joncker","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1600-065X.2006.00458.x","article-title":"Licensing of natural killer cells by self-major histocompatibility complex class I","volume":"214","author":"Yokoyama","year":"2006","journal-title":"Immunol. Rev."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2015.00368","article-title":"NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy","volume":"6","author":"Wang","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1002\/JLB.MR0718-269R","article-title":"Mechanisms of natural killer cell-mediated cellular cytotoxicity","volume":"105","author":"Prager","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/jso.23095","article-title":"High expression of CX3CL1 by tumor cells correlates with a good prognosis and increased tumor-infiltrating CD8+ T cells, natural killer cells, and dendritic cells in breast carcinoma","volume":"106","author":"Park","year":"2012","journal-title":"J. Surg. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4766","DOI":"10.1158\/0008-5472.CAN-15-1320","article-title":"Multiple myeloma impairs bone marrow localization of effector natural killer cells by altering the chemokine microenvironment","volume":"75","author":"Ponzetta","year":"2015","journal-title":"Cancer Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00262-016-1919-1","article-title":"High-efficiency lysis of cervical cancer by allogeneic NK cells derived from umbilical cord progenitors is independent of HLA status","volume":"66","author":"Veluchamy","year":"2017","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"289","DOI":"10.5732\/cjc.012.10063","article-title":"Expression of the CXCl12\/CXCR4 and CXCL16\/CXCR6 axes in cervical intraepithelial neoplasia and cervical cancer","volume":"32","author":"Huang","year":"2013","journal-title":"Chin. J. Cancer"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s40005-017-0381-1","article-title":"Recent challenges and advances in genetically-engineered cell therapy","volume":"48","author":"Yong","year":"2018","journal-title":"J. Pharm. Investig."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Mitchell, R.S., Beitzel, B.F., Schroder, A.R.W., Shinn, P., Chen, H., Berry, C.C., Ecker, J.R., and Bushman, F.D. (2004). Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences. PLoS Biol., 2.","DOI":"10.1371\/journal.pbio.0020234"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"6626","DOI":"10.1128\/JVI.00182-10","article-title":"Self-Inactivating Alpharetroviral Vectors with a Split-Packaging Design","volume":"84","author":"Suerth","year":"2010","journal-title":"J. Virol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"4811","DOI":"10.3390\/v6124811","article-title":"Alpharetroviral vectors: From a cancer-causing agent to a useful tool for human gene therapy","volume":"6","author":"Suerth","year":"2014","journal-title":"Viruses"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1600-065X.2008.00622.x","article-title":"Antigen-specific immunotherapy of cervical and ovarian cancer","volume":"222","author":"Hung","year":"2008","journal-title":"Immunol. Rev."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/0006-291X(87)90502-X","article-title":"Expression of chimeric receptor composed of immunoglobulin-derived V regions and T-cell receptor-derived C regions","volume":"149","author":"Kuwana","year":"1987","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.3389\/fimmu.2020.01965","article-title":"Use of Cell and Genome Modification Technologies to Generate Improved \u201cOff-the-Shelf\u201d CAR T and CAR NK Cells","volume":"11","author":"Morgan","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Paasch, D., Meyer, J., Stamopoulou, A., Lenz, D., Kuehle, J., Kloos, D., Buchegger, T., Holzinger, A., Falk, C.S., and Kloth, C. (2022). Ex Vivo Generation of CAR Macrophages from Hematopoietic Stem and Progenitor Cells for Use in Cancer Therapy. Cells, 11.","DOI":"10.3390\/cells11060994"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1126\/sciadv.aaz3223","article-title":"Chimeric antigen receptor signaling: Functional consequences and design implications","volume":"6","author":"Lindner","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1126\/scitranslmed.3005930","article-title":"CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia","volume":"5","author":"Brentjens","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0140-6736(14)61403-3","article-title":"T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: A phase 1 dose-escalation trial","volume":"385","author":"Lee","year":"2015","journal-title":"Lancet"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1242\/dmm.018036","article-title":"Genetically modified T cells in cancer therapy: Opportunities and challenges","volume":"8","author":"Sharpe","year":"2015","journal-title":"DMM Dis. Model. Mech."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1016\/j.celrep.2017.09.002","article-title":"Augmentation of Antitumor Immunity by Human and Mouse CAR T Cells Secreting IL-18","volume":"20","author":"Hu","year":"2017","journal-title":"Cell Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.1016\/j.celrep.2017.11.063","article-title":"CAR T Cells Releasing IL-18 Convert to T-Bethigh FoxO1low Effectors that Exhibit Augmented Activity against Advanced Solid Tumors","volume":"21","author":"Chmielewski","year":"2017","journal-title":"Cell Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"5697","DOI":"10.1158\/0008-5472.CAN-11-0103","article-title":"IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression","volume":"71","author":"Chmielewski","year":"2011","journal-title":"Cancer Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nbt.4086","article-title":"IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor","volume":"36","author":"Adachi","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/leu.2017.226","article-title":"Cord blood NK cells engineered to express IL-15 and a CD19- targeted CAR show long-term persistence and potent anti-tumor activity","volume":"32","author":"Liu","year":"2018","journal-title":"Leukemia"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"4173","DOI":"10.1128\/JVI.02546-13","article-title":"Human Papillomavirus E7 Oncoprotein Increases Production of the Anti-Inflammatory Interleukin-18 Binding Protein in Keratinocytes","volume":"88","author":"Richards","year":"2014","journal-title":"J. Virol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1158\/2159-8290.CD-17-1298","article-title":"Enhancing the potency and specificity of engineered T cells for cancer treatment","volume":"8","author":"Sukumaran","year":"2018","journal-title":"Cancer Discov"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.molimm.2012.03.023","article-title":"Tumor PD-L1 co-stimulates primary human CD8+ cytotoxic T cells modified to express a PD1: CD28 chimeric receptor","volume":"51","author":"Prosser","year":"2012","journal-title":"Mol. Immunol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nbt.4195","article-title":"Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo","volume":"36","author":"Rafiq","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/2162402X.2017.1368604","article-title":"mSA2 affinity-enhanced biotin-binding CAR T cells for universal tumor targeting","volume":"7","author":"Lohmueller","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1158\/0008-5472.CAN-11-3890","article-title":"A universal strategy for adoptive immunotherapy of cancer through use of a novel T cell antigen receptor","volume":"72","author":"Urbanska","year":"2012","journal-title":"Cancer Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/s43018-021-00244-2","article-title":"Dual-targeting CAR-T cells with optimal co-stimulation and metabolic fitness enhance antitumor activity and prevent escape in solid tumors","volume":"2","author":"Hirabayashi","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1038\/s41591-021-01436-0","article-title":"CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: A phase 1 trial","volume":"27","author":"Spiegel","year":"2021","journal-title":"Nat. Med."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1007\/s00262-019-02419-4","article-title":"Preclinical development of T-cell receptor-engineered T-cell therapy targeting the 5T4 tumor antigen on renal cell carcinoma","volume":"68","author":"Xu","year":"2019","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_139","first-page":"1","article-title":"Engineered TCR-T Cell Immunotherapy in Anticancer Precision Medicine: Pros and Cons","volume":"12","author":"Zhao","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"E2068","DOI":"10.1073\/pnas.1716266115","article-title":"Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity","volume":"115","author":"Davenport","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1038\/s41467-019-10097-0","article-title":"Synthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response","volume":"10","author":"Baeuerle","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2217\/imt-2019-0046","article-title":"Implications of T cell receptor biology on the development of new T cell therapies for cancer","volume":"12","author":"Hardy","year":"2020","journal-title":"Immunotherapy"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1038\/s41467-018-05395-y","article-title":"The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity","volume":"9","author":"Helsen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41421-018-0066-6","article-title":"A novel antibody-TCR (AbTCR) platform combines Fab-based antigen recognition with gamma\/delta-TCR signaling to facilitate T-cell cytotoxicity with low cytokine release","volume":"4","author":"Xu","year":"2018","journal-title":"Cell Discov."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Harper, J., Adams, K.J., Bossi, G., Wright, D.E., Stacey, A.R., Bedke, N., Martinez-Hague, R., Blat, D., Humbert, L., and Buchanan, H. (2018). An approved in vitro approach to preclinical safety and efficacy evaluation of engineered T cell receptor anti-CD3 bispecific (ImmTAC) molecules. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0205491"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"10713","DOI":"10.1038\/s41598-017-11126-y","article-title":"A TCR-based Chimeric Antigen Receptor","volume":"7","author":"Walseng","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"552028","DOI":"10.3389\/fpubh.2020.552028","article-title":"Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation","volume":"8","author":"Li","year":"2021","journal-title":"Front. Public Health"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"319","DOI":"10.4143\/crt.2005.37.6.319","article-title":"The Role of HPV E6 and E7 Oncoproteins in HPV-associated Cervical Carcinogenesis","volume":"37","author":"Yim","year":"2005","journal-title":"Cancer Res. Treat."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/jmv.1890370205","article-title":"Conservation of HPV-16 E6\/E7 ORF sequences in a cervical carcinoma","volume":"37","author":"Cone","year":"1992","journal-title":"J. Med. Virol."},{"key":"ref_150","first-page":"e99488","article-title":"Engineered t cells targeting E7 mediate regression of human papillomavirus cancers in a murine model","volume":"3","author":"Jin","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/s41591-020-01225-1","article-title":"TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers","volume":"27","author":"Nagarsheth","year":"2021","journal-title":"Nat. Med."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1200\/JCO.18.02424","article-title":"T-cell receptor gene therapy for human papillomavirus-associated epithelial cancers: A first-in-human, phase I\/II study","volume":"37","author":"Doran","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1126\/science.1208347","article-title":"Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice","volume":"334","author":"Michaud","year":"2011","journal-title":"Science"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/ncponc0666","article-title":"Increased intensity lymphodepletion and adoptive immunotherapy\u2014How far can we go?","volume":"3","author":"Muranski","year":"2006","journal-title":"Nat. Clin. Pract. Oncol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.coi.2009.03.002","article-title":"Adoptive Cell Therapy for the Treatment of Patients with Metastatic Melanoma Steven","volume":"21","author":"Rosenberg","year":"2009","journal-title":"Curr. Opin Immunol"},{"key":"ref_156","first-page":"2063","article-title":"Combination therapy: A feasibility strategy for car-t cell therapy in the treatment of solid tumors (review)","volume":"16","author":"Xu","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.4049\/jimmunol.1301119","article-title":"Synergistic Chemoimmunotherapy of Epithelial Ovarian Cancer Using ErbB-Retargeted T Cells Combined with Carboplatin","volume":"191","author":"Whilding","year":"2013","journal-title":"J. Immunol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S0360-3016(97)00372-6","article-title":"Effects of irradiation on the expression of major histocompatibility complex class I antigen and adhesion costimulation molecules ICAM-1 in human cervical cancer","volume":"39","author":"Santin","year":"1997","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.4049\/jimmunol.173.4.2462","article-title":"Ionizing Radiation Affects Human MART-1 Melanoma Antigen Processing and Presentation by Dendritic Cells","volume":"173","author":"Liao","year":"2004","journal-title":"J. Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Wan, S., Pestka, S., Jubin, R.G., Lyu, Y.L., Tsai, Y.C., and Liu, L.F. (2012). Chemotherapeutics and radiation stimulate MHC class i expression through elevated interferon-beta signaling in breast cancer cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032542"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"5416923","DOI":"10.1155\/2018\/5416923","article-title":"Cancer stem cells (CSCs) in drug resistance and their therapeutic implications in cancer treatment","volume":"2018","author":"Phi","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.pharmthera.2016.02.008","article-title":"Cancer Stem Cells and Chemoresistance: The Smartest Survives the Raid","volume":"160","author":"Zhao","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1089\/hum.2017.168","article-title":"Improved Killing of Ovarian Cancer Stem Cells by Combining a Novel Chimeric Antigen Receptor-Based Immunotherapy and Chemotherapy","volume":"28","author":"Klapdor","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/j.tranon.2018.08.005","article-title":"Chemotherapeutic Treatments Increase PD-L1 Expression in Esophageal Squamous Cell Carcinoma through EGFR\/ERK Activation","volume":"11","author":"Ng","year":"2018","journal-title":"Transl. Oncol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"5034","DOI":"10.1158\/0008-5472.CAN-14-3098","article-title":"Chemotherapy induces programmed cell death-ligand 1 overexpression via the nuclear factor-\u03baBto foster an immunosuppressive tumor microenvironment in Ovarian Cancer","volume":"75","author":"Peng","year":"2015","journal-title":"Cancer Res."},{"key":"ref_166","first-page":"5621","article-title":"Immune activation in patients with locally advanced cervical cancer treated with ipilimumab following definitive chemoradiation (GOG-9929)","volume":"26","author":"Enserro","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"(2017). Integrated genomic and molecular characterization of cervical cancer. Nature, 543, 378\u2013384.","DOI":"10.1038\/nature21386"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Evans, A.M., Salnikov, M., Tessier, T.M., and Mymryk, J.S. (2022). Reduced MHC Class I and II Expression in HPV-Negative vs. HPV-Positive Cervical Cancers. Cells, 11.","DOI":"10.3390\/cells11233911"},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Evans, A.M., Salnikov, M., Gameiro, S.F., Maleki Vareki, S., and Mymryk, J.S. (2022). HPV-Positive and -Negative Cervical Cancers Are Immunologically Distinct. J. Clin. Med., 11.","DOI":"10.3390\/jcm11164825"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"D\u2019Oria, O., Corrado, G., Lagan\u00e0, A.S., Chiantera, V., Vizza, E., and Giannini, A. (2022). New Advances in Cervical Cancer: From Bench to Bedside. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19127094"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Bogani, G., Lalli, L., Sopracordevole, F., Ciavattini, A., Ghelardi, A., Simoncini, T., Plotti, F., Casarin, J., Serati, M., and Pinelli, C. (2022). Development of a Nomogram Predicting the Risk of Persistence\/Recurrence of Cervical Dysplasia. Vaccines, 10.","DOI":"10.3390\/vaccines10040579"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1172\/JCI41004","article-title":"The therapeutic promise of the cancer stem cell concept","volume":"120","author":"Frank","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"e2022091118","DOI":"10.1073\/pnas.2022091118","article-title":"Hypoimmune induced pluripotent stem cell\u2013derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice","volume":"118","author":"Deuse","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/s41587-019-0016-3","article-title":"Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients","volume":"37","author":"Deuse","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1158\/1078-0432.CCR-16-1300","article-title":"Multiplex genome editing to generate universal CAR T cells resistant to PD1 inhibition","volume":"23","author":"Ren","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"eaba7365","DOI":"10.1126\/science.aba7365","article-title":"CRISPR-engineered T cells in patients with refractory cancer","volume":"367","author":"Stadtmauer","year":"2020","journal-title":"Science"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"3466","DOI":"10.1038\/s41375-021-01282-6","article-title":"Base-edited CAR T cells for combinational therapy against T cell malignancies","volume":"35","author":"Georgiadis","year":"2021","journal-title":"Leukemia"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.ymthe.2018.02.025","article-title":"Long Terminal Repeat CRISPR-CAR-Coupled \u201cUniversal\u201d T Cells Mediate Potent Anti-leukemic Effects","volume":"26","author":"Georgiadis","year":"2018","journal-title":"Mol. Ther."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/1\/263\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:48:47Z","timestamp":1760147327000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/1\/263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,30]]},"references-count":178,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["cancers15010263"],"URL":"https:\/\/doi.org\/10.3390\/cancers15010263","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,30]]}}}