{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:53:45Z","timestamp":1768352025953,"version":"3.49.0"},"reference-count":164,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Melanoma ranks as the fifth most common solid cancer in adults worldwide and is responsible for a significant proportion of skin-tumor-related deaths. The advent of immune checkpoint inhibition with anti-programmed death protein-1 (PD-1) antibodies has revolutionized the adjuvant treatment of high-risk, completely resected stage III\/IV melanoma. However, not all patients benefit equally. Current strategies for improving outcomes involve adjuvant treatment in earlier disease stages (IIB\/C) as well as perioperative treatment approaches. Interfering with T-cell exhaustion to counteract cancer immune evasion and the immunogenic nature of melanoma is key for anti-PD-1 effectiveness. Yet, the biological rationale for the efficacy of adjuvant treatment in clinically tumor-free patients remains to be fully elucidated. High-dose intermittent sun exposure (sunburn) is a well-known primary risk factor for melanomagenesis. Also, ultraviolet radiation (UVR)-induced immunosuppression may impair anti-cancer immune surveillance. In this review, we summarize the current knowledge about adjuvant anti-PD-1 blockade, including a characterization of the main cell types most likely responsible for its efficacy. In conclusion, we propose that local and systemic immunosuppression, to some extent UVR-mediated, can be restored by adjuvant anti-PD-1 therapy, consequently boosting anti-melanoma immune surveillance and the elimination of residual melanoma cell clones.<\/jats:p>","DOI":"10.3390\/cancers16081461","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T07:09:28Z","timestamp":1712819368000},"page":"1461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Adjuvant PD-1 Checkpoint Inhibition in Early Cutaneous Melanoma: Immunological Mode of Action and the Role of Ultraviolet Radiation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0210-5065","authenticated-orcid":false,"given":"Matthias","family":"Brandlmaier","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergology, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2771-4041","authenticated-orcid":false,"given":"Magdalena","family":"Hoellwerth","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5897-2780","authenticated-orcid":false,"given":"Peter","family":"Koelblinger","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9750-0188","authenticated-orcid":false,"given":"Roland","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7717-6125","authenticated-orcid":false,"given":"Andrea","family":"Harrer","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, Paracelsus Medical University, 5020 Salzburg, Austria"},{"name":"Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer Statistics","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ijc.33588","article-title":"Cancer statistics for the year 2020: An overview","volume":"149","author":"Ferlay","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S0025-6196(11)61033-1","article-title":"Malignant Melanoma in the 21st Century, Part 1: Epidemiology, Risk Factors, Screening, Prevention, and Diagnosis","volume":"82","author":"Markovic","year":"2007","journal-title":"Mayo Clin. Proc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1158\/1055-9965.EPI-04-0632","article-title":"Risk factors for melanoma by body site","volume":"14","author":"Cho","year":"2005","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1056\/NEJMra022137","article-title":"Skin Cancers after Organ Transplantation","volume":"348","author":"Euvrard","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1146\/annurev-pathol-012513-104658","article-title":"The molecular pathology of melanoma: An integrated taxonomy of melanocytic neoplasia","volume":"9","author":"Bastian","year":"2014","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1126\/science.1253735","article-title":"The melanoma revolution: From UV carcinogenesis to a new era in therapeutics","volume":"346","author":"Lo","year":"2014","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1046\/j.1365-2133.2001.04432.x","article-title":"Outdoor activities in childhood: A protective factor for cutaneous melanoma? Results of a case-control study in 271 matched pairs","volume":"145","author":"Kaskel","year":"2001","journal-title":"Br. J. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1001\/jamadermatol.2023.3256","article-title":"Stage-Specific Risk of Recurrence and Death from Melanoma in Denmark, 2008\u20132021","volume":"159","author":"Helvind","year":"2023","journal-title":"JAMA Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1080\/14737140.2018.1489246","article-title":"The eighth edition American Joint Committee on Cancer (AJCC) melanoma staging system: Implications for melanoma treatment and care","volume":"18","author":"Keung","year":"2018","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1200\/JCO.19.03034","article-title":"Prognosis of patients with stage III melanoma according to american joint committee on cancer version 8: A reassessment on the basis of 3 independent stage III melanoma cohorts","volume":"38","author":"Garbe","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3741","DOI":"10.1200\/JCO.22.00202","article-title":"Prognosis of Patients with Primary Melanoma Stage I and II According to American Joint Committee on Cancer Version 8 Validated in Two Independent Cohorts: Implications for Adjuvant Treatment","volume":"40","author":"Garbe","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1056\/NEJMoa1910836","article-title":"Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma","volume":"381","author":"Larkin","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1056\/NEJMoa1709030","article-title":"Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma","volume":"377","author":"Weber","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1016\/S0140-6736(22)00562-1","article-title":"Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): A randomised, double-blind, phase 3 trial","volume":"399","author":"Luke","year":"2022","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"s163","DOI":"10.25251\/skin.7.supp.163","article-title":"Adjuvant therapy with nivolumab versus placebo in patients with resected stage IIB\/C melanoma (CheckMate 76K)","volume":"7","author":"Long","year":"2023","journal-title":"Ski. J. Cutan. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.semcancer.2019.08.002","article-title":"Unraveling the crosstalk between melanoma and immune cells in the tumor microenvironment","volume":"59","author":"Marzagalli","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","article-title":"The repertoire of mutational signatures in human cancer","volume":"578","author":"Alexandrov","year":"2020","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1158\/0008-5472.CAN-14-3016","article-title":"IL10 and PD-1 cooperate to limit the activity of tumor-specific CD8+ T cells","volume":"75","author":"Sun","year":"2015","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1182\/blood-2008-12-195792","article-title":"Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired","volume":"114","author":"Ahmadzadeh","year":"2009","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/S1470-2045(20)30494-0","article-title":"Adjuvant nivolumab versus ipilimumab in resected stage IIIB\u2013C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial","volume":"21","author":"Ascierto","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ejca.2021.08.028","article-title":"Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for resected melanoma","volume":"158","author":"Weber","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1200\/JCO.20.02110","article-title":"Longer follow-up confirms recurrence-free survival benefit of adjuvant pembrolizumab in high-risk stage III melanoma: Updated results from the EORTC 1325-MG\/KEYNOTE-054 trial","volume":"38","author":"Eggermont","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"EVIDoa2200214","DOI":"10.1056\/EVIDoa2200214","article-title":"Five-Year Analysis of Adjuvant Pembrolizumab or Placebo in Stage III Melanoma","volume":"1","author":"Eggermont","year":"2022","journal-title":"NEJM Evid."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1056\/NEJMoa1802357","article-title":"Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma","volume":"378","author":"Eggermont","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3322\/caac.21409","article-title":"Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual","volume":"67","author":"Gershenwald","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1158\/1078-0432.CCR-22-3145","article-title":"Adjuvant Nivolumab versus Ipilimumab in Resected Stage III\/IV Melanoma: 5-Year Efficacy and Biomarker Results from CheckMate 238","volume":"29","author":"Larkin","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.annonc.2020.04.471","article-title":"Management of early melanoma recurrence despite adjuvant anti-PD-1 antibody therapy","volume":"31","author":"Owen","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e000398","DOI":"10.1136\/jitc-2019-000398","article-title":"Defining tumor resistance to PD-1 pathway blockade: Recommendations from the first meeting of the SITC Immunotherapy Resistance Taskforce","volume":"8","author":"Kluger","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/S1470-2045(22)00559-9","article-title":"Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma (KEYNOTE-716): Distant metastasis-free survival results of a multicentre, double-blind, randomised, phase 3 trial","volume":"23","author":"Long","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1200\/JCO.22.00533","article-title":"Adjuvant Therapy of Nivolumab Combined with Ipilimumab versus Nivolumab Alone in Patients with Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915)","volume":"41","author":"Weber","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"112914","DOI":"10.1016\/j.ejca.2023.05.003","article-title":"Adjuvant therapy for stage II melanoma: The need for further studies","volume":"189","author":"Lee","year":"2023","journal-title":"Eur. J. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"v533","DOI":"10.1093\/annonc\/mdz255","article-title":"Adjuvant nivolumab (NIVO) versus ipilimumab (IPI) in resected stage III\/IV melanoma: 3-year efficacy and biomarker results from the phase III CheckMate 238 trial","volume":"30","author":"Weber","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9502","DOI":"10.1200\/JCO.2018.36.15_suppl.9502","article-title":"Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III\/IV melanoma: Updated results from a phase III trial (CheckMate 238)","volume":"36","author":"Weber","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1158\/2159-8290.CD-21-1141","article-title":"Adjuvant Pembrolizumab versus IFN\u03b12b or Ipilimumab in Resected High-Risk Melanoma","volume":"12","author":"Grossmann","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Luke, J.J., Ascierto, P.A., Khattak, M.A., Merino, L.d.l.C., Del Vecchio, M., Rutkowski, P., Spagnolo, F., Mackiewicz, J., Chiarion-Sileni, V., and Kirkwood, J.M. (2024). Pembrolizumab versus Placebo as Adjuvant Therapy in Resected Stage IIB or IIC Melanoma: Final Analysis of Distant Metastasis-Free Survival in the Phase III KEYNOTE-716 Study. J. Clin. Oncol., JCO2302355.","DOI":"10.1200\/JCO.23.02355"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1158\/0008-5472.CAN-18-3134","article-title":"Upregulation of PD-L1 via HMGB1-activated IRF3 and NF-kB contributes to UV radiation-induced immune suppression","volume":"79","author":"Wang","year":"2019","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"106132","DOI":"10.18632\/oncotarget.22190","article-title":"Immune system and melanoma biology: A balance between immunosurveillance and immune escape","volume":"8","author":"Passarelli","year":"2017","journal-title":"Oncotarget"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0065-2776(08)60911-6","article-title":"Escape of human solid tumors from T\u2013cell recognition: Molecular mechanisms and functional significance","volume":"74","author":"Marincola","year":"2000","journal-title":"Adv. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6593","DOI":"10.1158\/1078-0432.CCR-14-0567","article-title":"Genetic evolution of T-cell resistance in the course of melanoma progression","volume":"20","author":"Sucker","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"101480","DOI":"10.1016\/j.smim.2021.101480","article-title":"Emerging concepts in PD-1 checkpoint biology","volume":"52","author":"Pauken","year":"2021","journal-title":"Semin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/s41590-022-01141-1","article-title":"A decade of checkpoint blockade immunotherapy in melanoma: Understanding the molecular basis for immune sensitivity and resistance","volume":"23","author":"Huang","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.immuni.2007.09.006","article-title":"Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection","volume":"27","author":"Wherry","year":"2007","journal-title":"Immunity"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.1128\/JVI.77.8.4911-4927.2003","article-title":"Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment","volume":"77","author":"Wherry","year":"2003","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nature10762","article-title":"Clonal evolution in cancer","volume":"481","author":"Greaves","year":"2012","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41577-021-00574-3","article-title":"CD8+ T cell differentiation and dysfunction in cancer","volume":"22","author":"Philip","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.immuni.2016.07.011","article-title":"Tumor-Specific T Cell Dysfunction Is a Dynamic Antigen-Driven Differentiation Program Initiated Early during Tumorigenesis","volume":"45","author":"Schietinger","year":"2016","journal-title":"Immunity"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.ccell.2018.03.012","article-title":"T Cell Dysfunction in Cancer","volume":"33","author":"Thommen","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nature22367","article-title":"Chromatin states define tumour-specific T cell dysfunction and reprogramming","volume":"545","author":"Philip","year":"2017","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1038\/s41590-021-00975-5","article-title":"Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation","volume":"22","author":"Manne","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/s41590-019-0312-6","article-title":"Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade","volume":"20","author":"Miller","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nature19330","article-title":"Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy","volume":"537","author":"Im","year":"2016","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/nature22079","article-title":"T-cell invigoration to tumour burden ratio associated with anti-PD-1 response","volume":"545","author":"Huang","year":"2017","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41586-020-2056-8","article-title":"Peripheral T cell expansion predicts tumour infiltration and clinical response","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1038\/s41591-019-0522-3","article-title":"Clonal replacement of tumor-specific T cells following PD-1 blockade","volume":"25","author":"Yost","year":"2019","journal-title":"Nat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1016\/j.immuni.2021.08.026","article-title":"Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes","volume":"54","author":"Schenkel","year":"2021","journal-title":"Immunity"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"eabg7836","DOI":"10.1126\/sciimmunol.abg7836","article-title":"A reservoir of stem-like CD8+ T cells in the tumor-draining lymph node preserves the ongoing antitumor immune response","volume":"6","author":"Connolly","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.ccell.2020.09.001","article-title":"The PD-1\/PD-L1-Checkpoint Restrains T cell Immunity in Tumor-Draining Lymph Nodes","volume":"38","author":"Dammeijer","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4049","DOI":"10.1016\/j.cell.2022.09.020","article-title":"The primordial differentiation of tumor-specific memory CD8+ T cells as bona fide responders to PD-1\/PD-L1 blockade in draining lymph nodes","volume":"185","author":"Huang","year":"2022","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1016\/j.immuni.2021.08.019","article-title":"Resident memory CD8+ T cells in regional lymph nodes mediate immunity to metastatic melanoma","volume":"54","author":"Molodtsov","year":"2021","journal-title":"Immunity"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1056\/NEJMoa2211437","article-title":"Neoadjuvant\u2013Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma","volume":"388","author":"Patel","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1093\/aje\/kwv282","article-title":"History of Severe Sunburn and Risk of Skin Cancer among Women and Men in 2 Prospective Cohort Studies","volume":"183","author":"Wu","year":"2016","journal-title":"Am. J. Epidemiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1038\/bjc.2014.43","article-title":"Cumulative ultraviolet radiation flux in adulthood and risk of incident skin cancers in women","volume":"110","author":"Wu","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1046\/j.1523-1747.2003.12246.x","article-title":"The influence of painful sunburns and lifetime sun exposure on the risk of actinic keratoses, seborrheic warts, melanocytic nevi, atypical nevi, and skin cancer","volume":"120","author":"Kennedy","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ejca.2004.10.016","article-title":"Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure","volume":"41","author":"Gandini","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/s41591-018-0265-6","article-title":"Ultraviolet radiation\u2013induced DNA damage is prognostic for outcome in melanoma","volume":"25","author":"Trucco","year":"2019","journal-title":"Nat. Med."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Ulisse, S., Baldini, E., Pironi, D., Gagliardi, F., Tripodi, D., Lauro, A., Carbotta, S., Tarroni, D., D\u2019armiento, M., and Morrone, A. (2022). Is Melanoma Progression Affected by Thyroid Diseases?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231710036"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/s41568-023-00565-7","article-title":"The journey from melanocytes to melanoma","volume":"23","author":"Centeno","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"ref_70","first-page":"651","article-title":"A Theory of the Etiology and Pathogenesis of Human Cutaneous Malignant Melanoma","volume":"71","author":"Holman","year":"1983","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1111\/bjd.19705","article-title":"Risk factors for melanoma by anatomical site: An evaluation of aetiological heterogeneity","volume":"184","author":"Laskar","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1001\/jamadermatol.2018.3964","article-title":"Association of Phenotypic Characteristics and UV Radiation Exposure with Risk of Melanoma on Different Body Sites","volume":"155","author":"Ghiasvand","year":"2019","journal-title":"JAMA Dermatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1002\/ijc.31527","article-title":"Global burden of cutaneous melanoma attributable to ultraviolet radiation in 2012","volume":"143","author":"Arnold","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrc.2016.37","article-title":"From melanocytes to melanomas","volume":"16","author":"Shain","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1007\/s43630-023-00375-8","article-title":"The effects of exposure to solar radiation on human health","volume":"22","author":"Neale","year":"2023","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/s41577-019-0185-9","article-title":"Photoimmunology: How ultraviolet radiation affects the immune system","volume":"19","author":"Bernard","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s00011-022-01598-8","article-title":"Photoaging: UV radiation-induced inflammation and immunosuppression accelerate the aging process in the skin","volume":"71","author":"Salminen","year":"2022","journal-title":"Inflamm. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1039\/c7pp00312a","article-title":"Ultraviolet radiation-induced immunosuppression and its relevance for skin carcinogenesis","volume":"17","author":"Hart","year":"2018","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Hughes, B.K., and Bishop, C.L. (2022). Current Understanding of the Role of Senescent Melanocytes in Skin Ageing. Biomedicines, 10.","DOI":"10.3390\/biomedicines10123111"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"694086","DOI":"10.3389\/fimmu.2021.694086","article-title":"More Than Effects in Skin: Ultraviolet Radiation-Induced Changes in Immune Cells in Human Blood","volume":"12","author":"Hart","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_81","first-page":"1345","article-title":"Biological effects of sunlight, ultraviolet radiation, visible light, infrared radiation and Vitamin D for health","volume":"36","author":"Holick","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jphotobiol.2018.06.005","article-title":"Ultraviolet radiation-mediated development of cutaneous melanoma: An update","volume":"185","author":"Emri","year":"2018","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"24196","DOI":"10.1073\/pnas.1907860116","article-title":"Genomic sites hypersensitive to ultraviolet radiation","volume":"116","author":"Premi","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1056\/NEJMoa1502583","article-title":"The Genetic Evolution of Melanoma from Precursor Lesions","volume":"373","author":"Shain","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e202101135","DOI":"10.26508\/lsa.202101135","article-title":"UVB mutagenesis differs in Nras- and Braf-mutant mouse models of melanoma","volume":"4","author":"Bowman","year":"2021","journal-title":"Life Sci. Alliance"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.1038\/s41467-022-31488-w","article-title":"Cutaneous and acral melanoma cross-OMICs reveals prognostic cancer drivers associated with pathobiology and ultraviolet exposure","volume":"13","author":"Vicente","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.7150\/thno.36218","article-title":"The \u2018ART\u2019 of epigenetics in melanoma: From histone \u2018alterations, to resistance and therapies\u2019","volume":"10","author":"Strub","year":"2020","journal-title":"Theranostics"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1056\/NEJMoa1503093","article-title":"Pembrolizumab versus Ipilimumab in Advanced Melanoma","volume":"372","author":"Robert","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/S1470-2045(15)00083-2","article-title":"Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): A randomised, controlled, phase 2 trial","volume":"16","author":"Ribas","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1242\/jcs.040667","article-title":"Melanosomes at a glance","volume":"121","author":"Wasmeier","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1111\/1523-1747.ep12607034","article-title":"Keratinocytes and fibroblasts in a human skin equivalent model enhance melanocyte survival and melanin synthesis after ultraviolet irradiation","volume":"104","author":"Archambault","year":"1995","journal-title":"J. Investig. Dermatol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"878336","DOI":"10.3389\/fonc.2022.878336","article-title":"Loss of \u2018Epidermal Melanin Unit\u2019 Integrity in Human Skin during Melanoma-Genesis","volume":"12","author":"Casalou","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_93","first-page":"481","article-title":"Das epidermale melanin-einheit-system","volume":"147","author":"Fitzpatrick","year":"1963","journal-title":"Dermatol. Wochenschr."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"51226","DOI":"10.1074\/jbc.M409768200","article-title":"UV-induced expression of key component of the tanning process, the POMC and MC1R genes, is dependent onp the p-38-activated upstream stimulating factor-1 (USF-1)","volume":"279","author":"Corre","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1038\/s41467-018-04086-y","article-title":"Genome-wide association study in 176,678 Europeans reveals genetic loci for tanning response to sun exposure","volume":"9","author":"Visconti","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/pcmr.12726","article-title":"MITF and UV responses in skin: From pigmentation to addiction","volume":"32","author":"Nguyen","year":"2019","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/bjd.20421","article-title":"Melanoma genomics: A state-of-the-art review of practical clinical applications","volume":"185","author":"Guhan","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Giunta, E.F., Arrichiello, G., Curvietto, M., Pappalardo, A., Bosso, D., Rosanova, M., Diana, A., Giordano, P., Petrillo, A., and Federico, P. (2021). Epigenetic regulation in melanoma: Facts and hopes. Cells, 10.","DOI":"10.3390\/cells10082048"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/ijc.29018","article-title":"MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: A pooled-analysis from the M-SKIP project","volume":"136","author":"Pasquali","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.2147\/CMAR.S155283","article-title":"MC1R variants as melanoma risk factors independent of at-risk phenotypic characteristics: A pooled analysis from the M-SKIP project","volume":"10","author":"Tagliabue","year":"2018","journal-title":"Cancer Manag. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5740","DOI":"10.1038\/s41467-023-41101-3","article-title":"Activation of melanocortin-1 receptor signaling in melanoma cells impairs T cell infiltration to dampen antitumor immunity","volume":"14","author":"Cui","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1146\/annurev-pathmechdis-012418-012809","article-title":"Exposure to Ultraviolet Radiation in the Modulation of Human Diseases","volume":"14","author":"Hart","year":"2019","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3389\/fmed.2018.00166","article-title":"A Perspective on the interplay of ultraviolet-radiation, skin microbiome and skin resident memory TCR\u03b1\u03b2+ cells","volume":"5","author":"Patra","year":"2018","journal-title":"Front. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5255","DOI":"10.1073\/pnas.94.10.5255","article-title":"The inhibition of antigen-presenting activity of dendritic cells resulting from UV irradiation of marine skin is restored by in vitro photorepair of cyclobutane pyrimidine dimers","volume":"94","author":"Vink","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1084\/jem.183.4.1491","article-title":"Localization of DNA damage and its role in altered antigen-presenting cell function in ultraviolet-irradiated mice","volume":"183","author":"Vink","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"485","DOI":"10.4049\/jimmunol.146.2.485","article-title":"Ultraviolet B radiation converts Langerhans cells from immunogenic to tolerogenic antigen-presenting cells. Induction of specific clonal anergy in CD4+ T helper 1 cells","volume":"146","author":"Simon","year":"1991","journal-title":"J. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2858","DOI":"10.1002\/eji.1830251022","article-title":"Low-dose UVB radiation perturbs the functional expression of B7.1 and B7.2 co-stimulatory molecules on human Langerhans cells","volume":"25","author":"Weiss","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gendis.2019.11.002","article-title":"Immune checkpoint molecules: \u201cNew\u201d kids on the block of skin photoimmunology","volume":"8","author":"Wang","year":"2021","journal-title":"Genes Dis."},{"key":"ref_109","first-page":"807","article-title":"A critical role for dermal mast cells in cis-urocanic acid-induced systemic suppression of contact hypersensitivity responses in mice","volume":"70","author":"Hart","year":"1999","journal-title":"Photochem. Photobiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4648","DOI":"10.4049\/jimmunol.180.7.4648","article-title":"Mast Cell Migration from the Skin to the Draining Lymph Nodes upon Ultraviolet Irradiation Represents a Key Step in the Induction of Immune Suppression","volume":"180","author":"Byrne","year":"2008","journal-title":"J. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1111\/j.0022-202X.2005.23615.x","article-title":"B cells activated in lymph nodes in response to ultraviolet irradiation or by interleukin-10 inhibit dendritic cell induction of immunity","volume":"124","author":"Byrne","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1365-2567.2010.03315.x","article-title":"Topical 1,25-dihydroxyvitamin D3 subverts the priming ability of draining lymph node dendritic cells","volume":"131","author":"Gorman","year":"2010","journal-title":"Immunology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/imm.12145","article-title":"Characterization of regulatory dendritic cells differentiated from the bone marrow of UV-irradiated mice","volume":"140","author":"Ng","year":"2013","journal-title":"Immunology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"394","DOI":"10.2741\/1807","article-title":"Spectral and dose dependence of ultraviolet radiation-induced immunosuppression","volume":"11","author":"Tai","year":"2006","journal-title":"Front. Biosci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1751-1097.2007.00212.x","article-title":"Waveband and dose dependency of sunlight-induced immunomodulation and cellular changes","volume":"84","author":"Halliday","year":"2008","journal-title":"Photochem. Photobiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/1523-1747.ep12613446","article-title":"Interleukin-10 production by cultured human keratinocytes: Regulation by ultraviolet B and ultraviolet A1 radiation","volume":"104","author":"Grewe","year":"1995","journal-title":"J. Investig. Dermatol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4049\/jimmunol.1001657","article-title":"Mast Cell-Derived IL-10 Suppresses Germinal Center Formation by Affecting T Follicular Helper Cell Function","volume":"186","author":"Ullrich","year":"2011","journal-title":"J. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.4049\/jimmunol.148.10.3072","article-title":"cis-urocanic acid suppression of contact hypersensitivity induction is mediated via tumor necrosis factor-alpha","volume":"148","author":"Kurimoto","year":"1992","journal-title":"J. Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"993","DOI":"10.2353\/ajpath.2008.070517","article-title":"Ultraviolet B suppresses immunity by inhibiting effector and memory T cells","volume":"172","author":"Rana","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/j.1751-1097.1997.tb01891.x","article-title":"Natural killer cell activity during UVR-induced skin tumor formation in the Skh hairless mouse","volume":"65","author":"Steerenberg","year":"1997","journal-title":"Photochem. Photobiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e1260215","DOI":"10.1080\/2162402X.2016.1260215","article-title":"Langerhans cells and NK cells cooperate in the inhibition of chemical skin carcinogenesis","volume":"6","author":"Ortner","year":"2017","journal-title":"OncoImmunology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1038\/s41591-018-0085-8","article-title":"A natural killer\u2013dendritic cell axis defines checkpoint therapy\u2013responsive tumor microenvironments","volume":"24","author":"Barry","year":"2018","journal-title":"Nat. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.cell.2018.01.004","article-title":"NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control","volume":"172","author":"Bonavita","year":"2018","journal-title":"Cell"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-642-19683-6_1","article-title":"Sensing the environment: Regulation of local and global homeostasis by the skin\u2019s neuroendocrine system","volume":"212","author":"Slominski","year":"2012","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/jid.2009.180","article-title":"TSH receptor and thyroid-specific gene expression in human skin","volume":"130","author":"Cianfarani","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Chen, Y.-Y., Liu, L.-P., Zhou, H., Zheng, Y.-W., and Li, Y.-M. (2022). Recognition of Melanocytes in Immuno-Neuroendocrinology and Circadian Rhythms: Beyond the Conventional Melanin Synthesis. Cells, 11.","DOI":"10.3390\/cells11132082"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/pcmr.13037","article-title":"The delicate relation between melanocytes and skin immunity: A game of hide and seek","volume":"35","author":"Speeckaert","year":"2022","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.smim.2009.03.002","article-title":"Skin immune surveillance by T cells\u2014A new order?","volume":"21","author":"Strid","year":"2009","journal-title":"Semin. Immunol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s12307-011-0065-8","article-title":"Cancer-immune equilibrium: Questions unanswered","volume":"4","author":"Bhatia","year":"2011","journal-title":"Cancer Microenviron."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/B978-0-12-800267-4.00003-1","article-title":"Recognition of tumors by the innate immune system and natural killer cells","volume":"122","author":"Marcus","year":"2014","journal-title":"Adv. Immunol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Maglio, D.H.G., Paz, M.L., and Leoni, J. (2016). Sunlight Effects on Immune System: Is There Something Else in addition to UV-Induced Immunosuppression?. BioMed Res. Int., 2016.","DOI":"10.1155\/2016\/1934518"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e01104","DOI":"10.1002\/cti2.1104","article-title":"UV radiation recruits CD4+GATA3+ and CD8+GATA3+ T cells while altering the lipid microenvironment following inflammatory resolution in human skin in vivo","volume":"9","author":"Hawkshaw","year":"2020","journal-title":"Clin. Transl. Immunol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/exd.12363","article-title":"How, and from which cell sources, do nevi really develop?","volume":"23","author":"Grichnik","year":"2014","journal-title":"Exp. Dermatol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"E2","DOI":"10.1038\/skinbio.2013.176","article-title":"Photoaging","volume":"133","author":"Gilchrest","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Saginala, K., Barsouk, A., Aluru, J.S., Rawla, P., and Barsouk, A. (2021). Epidemiology of Melanoma. Med. Sci., 9.","DOI":"10.3390\/medsci9040063"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","article-title":"The senescence-associated secretory phenotype: The dark side of tumor suppression","volume":"5","author":"Desprez","year":"2010","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging: An evolutionary perspective on immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"100998","DOI":"10.1016\/j.arr.2019.100998","article-title":"Activation of immunosuppressive network in the aging process","volume":"57","author":"Salminen","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/s41586-018-0812-9","article-title":"Tissue-resident memory CD8+ T cells promote melanoma\u2013immune equilibrium in skin","volume":"565","author":"Park","year":"2019","journal-title":"Nature"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1158\/0008-5472.CAN-03-3066","article-title":"Effector Function of Human Tumor-Specific CD8 T Cells in Melanoma Lesions: A State of Local Functional Tolerance","volume":"64","author":"Zippelius","year":"2004","journal-title":"Cancer Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1158\/2326-6066.CIR-16-0001","article-title":"Tumor- and neoantigen-reactive T-cell receptors can be identified based on their frequency in fresh tumor","volume":"4","author":"Pasetto","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/nm.4051","article-title":"Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients","volume":"22","author":"Gros","year":"2016","journal-title":"Nat. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1172\/JCI82416","article-title":"Isolation of neoantigen-specific T cells from tumor and peripheral lymphocytes","volume":"125","author":"Cohen","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"4992","DOI":"10.1172\/JCI127967","article-title":"Recognition of human gastrointestinal cancer neoantigens by circulating PD-1+ lymphocytes","volume":"129","author":"Gros","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1158\/0008-5472.CAN-19-0839","article-title":"Deciphering mechanisms of UVR-induced tumoral immune checkpoint regulation against melanoma","volume":"79","author":"Sahu","year":"2019","journal-title":"Cancer Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1200\/PO.21.00084","article-title":"Positive Association btween Location of Melanoma, Ultraviolet Signature, Tumor Mutational Burden, and Response to Anti\u2013PD-1 Therapy","volume":"5","author":"Dousset","year":"2021","journal-title":"JCO Precis. Oncol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nature24673","article-title":"Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth","volume":"552","author":"Germano","year":"2017","journal-title":"Nature"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nature13988","article-title":"Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens","volume":"515","author":"Gubin","year":"2014","journal-title":"Nature"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1126\/science.aaf2288","article-title":"Targeting of cancer neoantigens with donor-derived T cell receptor repertoires","volume":"352","author":"Toebes","year":"2016","journal-title":"Science (80-)"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.cell.2019.08.032","article-title":"UVB-Induced Tumor Heterogeneity Diminishes Immune Response in Melanoma","volume":"179","author":"Wolf","year":"2019","journal-title":"Cell"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1126\/science.aaf1490","article-title":"Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade","volume":"351","author":"McGranahan","year":"2016","journal-title":"Science"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/s41588-018-0200-2","article-title":"Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors","volume":"50","author":"Miao","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/S0140-6736(23)02268-7","article-title":"Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): A randomised, phase 2b study","volume":"403","author":"Weber","year":"2024","journal-title":"Lancet"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/s41591-022-02163-w","article-title":"Persistent mutation burden drives sustained anti-tumor immune responses","volume":"29","author":"Niknafs","year":"2023","journal-title":"Nat. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.cell.2014.12.033","article-title":"Molecular and Genetic properties of tumors associated with local immune cytolytic activity","volume":"160","author":"Rooney","year":"2015","journal-title":"Cell"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.it.2016.04.008","article-title":"Tumor Heterogeneity and Tumor Immunity: A Chicken-and-Egg Problem","volume":"37","author":"Spranger","year":"2016","journal-title":"Trends Immunol."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Rosenthal, R., McGranahan, N., Herrero, J., Taylor, B.S., and Swanton, C. (2016). deconstructSigs: Delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution. Genome Biol., 17.","DOI":"10.1186\/s13059-016-0893-4"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41525-017-0013-8","article-title":"Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma","volume":"2","author":"Reuben","year":"2017","journal-title":"npj Genom. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"571545","DOI":"10.3389\/fonc.2020.571545","article-title":"Integration of the Tumor Mutational Burden and Tumor Heterogeneity Identify an Immunological Subtype of Melanoma with Favorable Survival","volume":"10","author":"Gao","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.cell.2017.01.018","article-title":"Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future","volume":"168","author":"McGranahan","year":"2017","journal-title":"Cell"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"eaat1435","DOI":"10.1126\/sciimmunol.aat1435","article-title":"The immune system profoundly restricts intratumor genetic heterogeneity","volume":"3","author":"Milo","year":"2018","journal-title":"Sci. Immunol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"eabd8636","DOI":"10.1126\/scitranslmed.abd8636","article-title":"Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses","volume":"13","author":"Lo","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1001\/jamadermatol.2015.2707","article-title":"Association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab","volume":"152","author":"Hua","year":"2016","journal-title":"JAMA Dermatol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/8\/1461\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:26:12Z","timestamp":1760106372000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/8\/1461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,11]]},"references-count":164,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["cancers16081461"],"URL":"https:\/\/doi.org\/10.3390\/cancers16081461","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,11]]}}}