{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T03:44:47Z","timestamp":1785469487533,"version":"3.56.0"},"reference-count":97,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T00:00:00Z","timestamp":1619222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1F1A1073833"],"award-info":[{"award-number":["2020R1F1A1073833"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Renal cell carcinoma (RCC) is a malignant tumor associated with various tumor microenvironments (TMEs). The immune system is activated by the development of cancer and drives T cell anti-tumor response. CD8 T cells are known to improve clinical outcomes and sensitivity to immunotherapy, and play a crucial role against tumors. In contrast, tumor-associated macrophages (TAMs) suppress immunity against malignancy and lead to tumor progression. TAMs are promoted from damaged TMEs and mount proinflammatory responses to pathogens. Initial immunotherapy consists of interferon-\u03b1 and interleukin-2. However, response to such therapy is unclear in most patients, and it is associated with high levels of toxicity. Immune checkpoint inhibitors (ICIs), which up-regulate immune responses by blocking the programed cell death protein 1 (PD-1) receptor, the ligand of PD-1, or cytotoxic T-lymphocyte-associated protein 4 T cells, have led to a new era of immunotherapy. Furthermore, combination strategies with ICIs have proven effective through several randomized controlled trials. We expect the next generation of immunotherapy to lead to better outcomes based on ongoing trials and inspire new therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms22094452","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T21:49:20Z","timestamp":1619300960000},"page":"4452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Immunology and Immunotherapeutic Approaches for Advanced Renal Cell Carcinoma: A Comprehensive Review"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6424-4619","authenticated-orcid":false,"given":"Yoon-Soo","family":"Hah","sequence":"first","affiliation":[{"name":"Department of Urology, Catholic University of Daegu School of Medicine, Daegu 42472, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7303-6256","authenticated-orcid":false,"given":"Kyo-Chul","family":"Koo","sequence":"additional","affiliation":[{"name":"Department of Urology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06229, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1101\/gr.131110.111","article-title":"Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics","volume":"22","author":"Linehan","year":"2012","journal-title":"Genome Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1126\/science.8493574","article-title":"Identification of the von hippel-lindau disease tumor suppressor gene","volume":"260","author":"Latif","year":"1993","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nature12222","article-title":"Comprehensive molecular characterization of clear cell renal cell carcinoma","volume":"499","author":"Network","year":"2013","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/nrc2502","article-title":"The von hippel\u2013lindau tumour suppressor protein: O2 sensing and cancer","volume":"8","author":"Kaelin","year":"2008","journal-title":"Nat. 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