{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:50Z","timestamp":1787027810338,"version":"build-2736575974"},"reference-count":94,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,17]],"date-time":"2024-03-17T00:00:00Z","timestamp":1710633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004418","name":"VUB strategic research program","doi-asserted-by":"publisher","award":["SRP89"],"award-info":[{"award-number":["SRP89"]}],"id":[{"id":"10.13039\/501100004418","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>In recent years, immune checkpoint inhibitors (ICIs) have become a viable option for many cancer patients, including specific subgroups of pediatric patients. Despite their efficiency in treating different types of cancer, ICIs are responsible for a number of immune-related adverse events, including inflammatory toxicities, that can affect several organs. However, our knowledge of the impact of ICIs on the testis and male fertility is limited. It is possible that ICI treatment affects testicular function and spermatogenesis either directly or indirectly (or both). Treatment with ICIs may cause increased inflammation and immune cell infiltration within the seminiferous tubules of the testis, disturbing spermatogenesis or testosterone deficiency (primary hypogonadism). Additionally, the interference of ICIs with the hypothalamic\u2013pituitary\u2013gonadal axis may alter testosterone production, affecting testicular function (secondary hypogonadism) and spermatogenesis. This review provides an overview of the available evidence on the potential association between ICIs and the disruption of spermatogenesis, with special focus on ICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1). Moreover, it highlights the need for further investigations and encourages the discussion of associated risks and fertility-preservation considerations between clinicians and patients.<\/jats:p>","DOI":"10.3390\/cancers16061176","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T04:25:15Z","timestamp":1710735915000},"page":"1176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Immune Checkpoint Inhibitors and Male Fertility: Should Fertility Preservation Options Be Considered before Treatment?"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7922-7034","authenticated-orcid":false,"given":"Elissavet","family":"Ntemou","sequence":"first","affiliation":[{"name":"Genetics, Reproduction and Development (GRAD) Research Group, Biology of the Testis (BITE) Team, Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-2173","authenticated-orcid":false,"given":"Emily","family":"Delgouffe","sequence":"additional","affiliation":[{"name":"Genetics, Reproduction and Development (GRAD) Research Group, Biology of the Testis (BITE) Team, Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7601-9689","authenticated-orcid":false,"given":"Ellen","family":"Goossens","sequence":"additional","affiliation":[{"name":"Genetics, Reproduction and Development (GRAD) Research Group, Biology of the Testis (BITE) Team, Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.7150\/jca.24577","article-title":"Current status and future directions of cancer immunotherapy","volume":"9","author":"Zhang","year":"2018","journal-title":"J. Canc."},{"key":"ref_2","first-page":"e1041","article-title":"2018 Nobel Prize in physiology or medicine","volume":"7","author":"Smyth","year":"2018","journal-title":"CTI"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1056\/NEJMra1703481","article-title":"Immune-related adverse events associated with immune checkpoint blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1016\/S1470-2045(20)30582-9","article-title":"Fertility preservation for male patients with childhood, adolescent, and young adult cancer: Recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group","volume":"22","author":"Mulder","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/328267a0","article-title":"A new member of the immunoglobulin superfamily\u2014CTLA-4","volume":"328","author":"Brunet","year":"1987","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ijrobp.2012.12.025","article-title":"Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas","volume":"86","author":"Zeng","year":"2013","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nri.2017.108","article-title":"The diverse functions of the PD1 inhibitory pathway","volume":"18","author":"Sharpe","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.7555\/JBR.31.20160168","article-title":"Immune checkpoint inhibitors in cancer therapy","volume":"32","author":"Webb","year":"2018","journal-title":"J. Biomed. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1158\/2159-8290.CD-18-0367","article-title":"Fundamental mechanisms of immune checkpoint blockade therapy","volume":"8","author":"Wei","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/cei.13255","article-title":"Immunotherapies based on PD-1\/PD-L1 pathway inhibitors in ovarian cancer treatment","volume":"195","author":"Suszczyk","year":"2019","journal-title":"Clin. Exp. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/ni0702-611","article-title":"CTLA-4: New insights into its biological function and use in tumor immunotherapy","volume":"3","author":"Egen","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nrd.2015.35","article-title":"Development of immuno-oncology drugs\u2014From CTLA4 to PD1 to the next generations","volume":"15","author":"Hoos","year":"2016","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1016\/j.cell.2023.03.006","article-title":"Immune checkpoint therapy-current perspectives and future directions","volume":"186","author":"Sharma","year":"2023","journal-title":"Cell"},{"key":"ref_15","unstructured":"(2024, January 23). ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Vaddepally, R.K., Kharel, P., Pandey, R., Garje, R., and Chandra, A.B. (2020). Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence. Cancers, 12.","DOI":"10.3390\/cancers12030738"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"736123","DOI":"10.3389\/fonc.2021.736123","article-title":"Immunotherapy in adolescents and young adults: What remains in cancer survivors?","volume":"11","author":"Tanda","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_18","first-page":"579","article-title":"Immune checkpoint inhibitor therapy in oncology: Current uses and future directions","volume":"4","author":"Tan","year":"2022","journal-title":"Cardio Oncol."},{"key":"ref_19","unstructured":"(2024, January 11). Drugs@FDA: FDA-Approved Drugs, Available online: https:\/\/www.accessdata.fda.gov\/scripts\/cder\/daf\/index.cfm."},{"key":"ref_20","unstructured":"(2024, January 11). Pediatric Oncology Drug Approvals, Available online: https:\/\/www.fda.gov\/about-fda\/oncology-center-excellence\/pediatric-oncology-drug-approvals."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.semcdb.2016.01.019","article-title":"Testicular immunoregulation and spermatogenesis","volume":"59","author":"Chen","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/cmi.2014.38","article-title":"Testicular defense systems: Immune privilege and innate immunity","volume":"11","author":"Zhao","year":"2014","journal-title":"Cell. Mol. Immunol."},{"key":"ref_23","first-page":"309","article-title":"Immunoregulation in the testis and its implication in fertility and infections","volume":"1","author":"Khambata","year":"2021","journal-title":"Explor. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1124\/pr.110.002790","article-title":"The blood\u2013testis barrier and its implications for male contraception","volume":"64","author":"Cheng","year":"2012","journal-title":"Pharmacol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/978-1-60761-869-0_29","article-title":"Immunoprivileged sites: The testis","volume":"677","author":"Fijak","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"583304","DOI":"10.3389\/fimmu.2020.583304","article-title":"Immune cell subtypes and their function in the testis","volume":"11","author":"Bhushan","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0165-0378(02)00016-5","article-title":"Macrophages and the immune responsiveness of the testis","volume":"57","author":"Hedger","year":"2002","journal-title":"J. Reprod. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4327","DOI":"10.4049\/jimmunol.1700162","article-title":"Characterization of the micro-environment of the testis that shapes the phenotype and function of testicular macrophages","volume":"198","author":"Wang","year":"2017","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1189\/jlb.1010557","article-title":"Rat resident testicular macrophages have an alternatively activated phenotype and constitutively produce interleukin-10 in vitro","volume":"90","author":"Winnall","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.cellimm.2018.03.009","article-title":"Testicular macrophages: Guardians of fertility","volume":"330","author":"Sieweke","year":"2018","journal-title":"Cell. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/molehr\/gam067","article-title":"Expression of co-stimulatory molecules, chemokine receptors and proinflammatory cytokines in dendritic cells from normal and chronically inflamed rat testis","volume":"13","author":"Rival","year":"2007","journal-title":"Mol. Hum. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e536","DOI":"10.1111\/j.1365-2605.2010.01137.x","article-title":"Immunodeviation towards a Th17 immune response associated with testicular damage in azoospermic men","volume":"34","author":"Duan","year":"2011","journal-title":"Int. J. Androl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1586\/eci.11.57","article-title":"The role of mast cells in male infertility","volume":"7","author":"Haidl","year":"2011","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e13055","DOI":"10.1111\/and.13055","article-title":"Human testicular peritubular cells, mast cells and testicular inflammation","volume":"50","author":"Mayerhofer","year":"2018","journal-title":"Andrologia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"112","DOI":"10.4103\/aja.aja_30_19","article-title":"Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord","volume":"22","author":"Moreno","year":"2020","journal-title":"Asian J. Androl."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/bs.ircmb.2018.05.008","article-title":"T lymphocytes and autoimmunity","volume":"341","author":"Khan","year":"2018","journal-title":"Int. Rev. Cell. Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1530\/ror.0.0020038","article-title":"Testicular leukocytes: What are they doing?","volume":"2","author":"Hedger","year":"1997","journal-title":"Rev. Reprod."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Gong, J., Zeng, Q., Yu, D., and Duan, Y.G. (2020). T lymphocytes and testicular immunity: A new insight into immune regulation in testes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010057"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3982","DOI":"10.4049\/jimmunol.164.8.3982","article-title":"Persistence of physiological self-antigen is required for the regulation of self-tolerance","volume":"164","author":"Garza","year":"2000","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7511","DOI":"10.1073\/pnas.1017615108","article-title":"Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy","volume":"108","author":"Wheeler","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6161","DOI":"10.4049\/jimmunol.174.10.6161","article-title":"Testicular immune privilege promotes transplantation tolerance by altering the balance between memory and regulatory T cells","volume":"174","author":"Nasr","year":"2005","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jri.2009.04.005","article-title":"Differential changes in CD4+ and CD8+ effector and regulatory T lymphocyte subsets in the testis of rats undergoing autoimmune orchitis","volume":"81","author":"Jacobo","year":"2009","journal-title":"J. Reprod. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e13092","DOI":"10.1111\/and.13092","article-title":"The role of regulatory T Cells in autoimmune orchitis","volume":"50","author":"Jacobo","year":"2018","journal-title":"Andrologia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1530\/REP-10-0362","article-title":"CD4+ and CD8+ T cells producing Th1 and Th17 cytokines are involved in the pathogenesis of autoimmune orchitis","volume":"141","author":"Jacobo","year":"2011","journal-title":"Reproduction"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0165-0378(00)00071-1","article-title":"Local regulation of T cell numbers and lymphocyte-inhibiting activity in the interstitial tissue of the adult rat testis","volume":"48","author":"Hedger","year":"2000","journal-title":"J. Reprod. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.mce.2011.09.031","article-title":"Regulation of activin and inhibin in the adult testis and the evidence for functional roles in spermatogenesis and immunoregulation","volume":"359","author":"Hedger","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.2337\/diabetes.49.11.1810","article-title":"Testicular Sertoli cells protect islet beta-cells from autoimmune destruction in NOD mice by a transforming growth factor-beta1-dependent mechanism","volume":"49","author":"Korbutt","year":"2000","journal-title":"Diabetes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.mce.2012.10.016","article-title":"Damaged spermatogenic cells induce inflammatory gene expression in mouse Sertoli cells through the activation of Toll-like receptors 2 and 4","volume":"365","author":"Zhang","year":"2013","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5162","DOI":"10.4049\/jimmunol.1001958","article-title":"Testosterone replacement effectively inhibits the development of experimental autoimmune orchitis in rats: Evidence for a direct role of testosterone on regulatory T cell expansion","volume":"186","author":"Fijak","year":"2011","journal-title":"J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"37128","DOI":"10.1038\/srep37128","article-title":"Sterile inflammation as a factor in human male infertility: Involvement of Toll-like receptor 2, biglycan and peritubular cells","volume":"6","author":"Mayer","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"R19","DOI":"10.1016\/0303-7207(94)90177-5","article-title":"The mature form of interleukin-1 alpha is constitutively expressed in immature male germ cells from rat","volume":"105","author":"Haugen","year":"1994","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ando.2014.03.001","article-title":"Mini-puberty and true puberty: Differences in testicular function","volume":"75","author":"Rey","year":"2014","journal-title":"Ann. Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Oatley, J.M., and Griswold, M.D. (2017). The Biology of Mammalian Spermatogonia, Springer Press. [1st ed.].","DOI":"10.1007\/978-1-4939-7505-1"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1530\/REP-09-0255","article-title":"Spermatogonial stem cells in higher primates: Are there differences from those in rodents?","volume":"139","author":"Hermann","year":"2010","journal-title":"Reproduction"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1530\/rep.0.1250769","article-title":"Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood","volume":"125","author":"Sharpe","year":"2003","journal-title":"Reproduction"},{"key":"ref_56","first-page":"2325","article-title":"Spermatogenesis","volume":"Volume 3","author":"Jameson","year":"2016","journal-title":"Endocrinology: Adult and Pediatric"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1146\/annurev.immunol.26.021607.090331","article-title":"PD-1 and its ligands in tolerance and immunity","volume":"26","author":"Keir","year":"2008","journal-title":"Annu. Rev. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1097\/TP.0b013e3181a75633","article-title":"Interaction of programmed death-1 and programmed death-1 ligand-1 contributes to testicular immune privilege","volume":"87","author":"Cheng","year":"2009","journal-title":"Transplantation"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1095\/biolreprod.107.063578","article-title":"Mouse Sertoli cells display phenotypical and functional traits of antigen-presenting cells in response to interferon gamma","volume":"78","author":"Riccioli","year":"2008","journal-title":"Biol. Reprod."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e13079","DOI":"10.1111\/aji.13079","article-title":"Identification of programmed cell death 1 and its ligand in the testicular tissue of mice","volume":"81","author":"Wang","year":"2019","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s11912-015-0479-4","article-title":"Emerging therapeutic targets for male germ cell tumors","volume":"17","author":"Fankhauser","year":"2015","journal-title":"Curr. Oncol. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1093\/annonc\/mdv574","article-title":"Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors","volume":"27","author":"Cierna","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_63","first-page":"9852","article-title":"Increased tumor vascularization is associated with the amount of immune competent PD-1 positive cells in testicular germ cell tumors","volume":"15","author":"Jennewein","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1111\/jcmm.17305","article-title":"Overexpression of PD-L1 causes germ cells to slough from mouse seminiferous tubules via the PD-L1\/PD-L1 interaction","volume":"26","author":"Fang","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.stemcr.2023.02.008","article-title":"Allogeneic offspring produced by induction of PD-L1 in spermatogonial stem cells via self-renewal stimulation","volume":"18","author":"Shinohara","year":"2023","journal-title":"Stem Cell Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"100276","DOI":"10.1016\/j.esmoop.2021.100276","article-title":"Checkpoint inhibitors, fertility, pregnancy, and sexual life: A systematic review","volume":"6","author":"Garutti","year":"2021","journal-title":"ESMO Open"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s12094-021-02699-2","article-title":"Multidisciplinary consensus on the criteria for fertility preservation in cancer patients","volume":"24","author":"Santaballa","year":"2022","journal-title":"Clin. Transl. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1001\/jamaoncol.2020.1641","article-title":"Association of impaired spermatogenesis with the use of immune checkpoint inhibitors in patients with metastatic melanoma","volume":"6","author":"Scovell","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"101488","DOI":"10.1016\/j.eucr.2020.101488","article-title":"Onset of azoospermia in man treated with ipilimumab\/nivolumab for BRAF negative metastatic melanoma","volume":"34","author":"Rabinowitz","year":"2020","journal-title":"Urol. Case Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ejca.2021.04.031","article-title":"Male fertility during and after immune checkpoint inhibitor therapy: A cross-sectional pilot study","volume":"152","author":"Salzmann","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e002220","DOI":"10.1136\/jitc-2020-002220","article-title":"Immune checkpoint inhibitor-related hypogonadism and infertility: A neglected issue in immuno-oncology","volume":"9","year":"2021","journal-title":"J. ImmunoTher. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1093\/annonc\/mdw696","article-title":"Immune checkpoint inhibitors-related orchitis","volume":"28","author":"Opsomer","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1634\/theoncologist.2018-0722","article-title":"Severe epididymo-orchitis and encephalitis complicating anti-PD-1 therapy","volume":"24","author":"Quach","year":"2019","journal-title":"Oncologist"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1530\/ERC-13-0499","article-title":"Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: A comprehensive retrospective review from a single institution","volume":"21","author":"Ryder","year":"2014","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2042018819896182","DOI":"10.1177\/2042018819896182","article-title":"Immunotherapy-induced endocrinopathies: Assessment, management, and monitoring","volume":"10","author":"Nogueira","year":"2019","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1007\/s12020-020-02355-9","article-title":"Mapping endocrine toxicity spectrum of immune checkpoint inhibitors: A disproportionality analysis using the WHO adverse drug reaction database, VigiBase","volume":"69","author":"Bai","year":"2020","journal-title":"Endocrine"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ctrv.2016.02.003","article-title":"Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy","volume":"45","author":"Eigentler","year":"2016","journal-title":"Cancer Treat. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ctrv.2017.05.003","article-title":"Combined immune checkpoint blockade (anti-PD-1\/anti-CTLA-4): Evaluation and management of adverse drug reactions","volume":"57","author":"Hassel","year":"2017","journal-title":"Cancer Treat. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4078","DOI":"10.1210\/jc.2014-2306","article-title":"Ipilimumab-induced hypophysitis: A detailed longitudinal analysis in a large cohort of patients with metastatic melanoma","volume":"99","author":"Faje","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1530\/EJE-14-0845","article-title":"Long-Term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma","volume":"172","author":"Albarel","year":"2015","journal-title":"Eur. J. Endocrinol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1001\/jamaoncol.2017.3064","article-title":"Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: A systematic review and meta-analysis","volume":"4","author":"Barry","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"19419","DOI":"10.1038\/s41598-019-56026-5","article-title":"mmune checkpoint inhibitors-induced hypophysitis: A retrospective analysis of the French Pharmacovigilance database","volume":"9","author":"Petitpain","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"199","DOI":"10.18632\/oncotarget.27876","article-title":"Testosterone deficiency in men receiving immunotherapy for malignant melanoma","volume":"12","author":"Peters","year":"2021","journal-title":"Oncotarget"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"pkz008","DOI":"10.1093\/jncics\/pkz008","article-title":"Cancer treatment-related infertility: A critical review of the evidence","volume":"3","author":"Poorvu","year":"2019","journal-title":"JNCI Cancer Spectr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.fertnstert.2013.08.010","article-title":"Effects of chemotherapy and radiotherapy on spermatogenesis in humans","volume":"100","author":"Meistrich","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"854186","DOI":"10.3389\/fendo.2022.854186","article-title":"Testicular tissue banking for fertility preservation in young boys: Which patients should be included?","volume":"13","author":"Delgouffe","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1093\/humrep\/dev190","article-title":"A European perspective on testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys","volume":"30","author":"Picton","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"hoaa016","DOI":"10.1093\/hropen\/hoaa016","article-title":"Fertility preservation in boys: Recent developments and new insights","volume":"2020","author":"Goossens","year":"2020","journal-title":"Hum. Reprod. Open"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Cosci, I., Grande, G., Di Nisio, A., Rocca, M.S., Del Fiore, P., Benna, C., Mocellin, S., and Ferlin, A. (2022). Cutaneous Melanoma and hormones: Focus on sex differences and the testis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010599"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1001\/jama.1988.03720140043031","article-title":"The relationship of gonadal activity and chemotherapy-induced gonadal damage","volume":"259","author":"Rivkees","year":"1988","journal-title":"JAMA"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Rommerts, F.F.G., and Teerds, K.J. (2002). Testicular Tangrams, Springer Press. [1st ed.].","DOI":"10.1007\/978-3-662-05066-8"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.beem.2010.09.007","article-title":"Testicular function and fertility preservation in male cancer patients","volume":"25","author":"Jahnukainen","year":"2011","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1093\/humrep\/17.12.3157","article-title":"Semen quality and cryopreservation in adolescent cancer patients","volume":"17","author":"Bahadur","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1093\/humrep\/deq147","article-title":"Clinical and biochemical correlates of successful semen collection for cryopreservation from 12-18-year-old patients: A single-center study of 86 adolescents","volume":"25","author":"Rechnitzer","year":"2010","journal-title":"Hum. Reprod."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/6\/1176\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:14:54Z","timestamp":1760105694000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/6\/1176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,17]]},"references-count":94,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["cancers16061176"],"URL":"https:\/\/doi.org\/10.3390\/cancers16061176","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,17]]}}}