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PMID: 33746989 Published · epublish English Journal Article Research Support, Non-U.S. Gov't Review

Roles of the Dynamic Tumor Immune Microenvironment in the Individualized Treatment of Advanced Clear Cell Renal Cell Carcinoma.

Frontiers in immunology ·Vol. 12 ·2021-00-00 ·Pages 653358

Lin E, Liu X, Liu Y, Zhang Z, Xie L, Tian K, Liu J, Yu Y

Abstract

Immune checkpoint inhibitors (ICIs) are currently a first-line treatment option for clear cell renal cell carcinoma (ccRCC). However, recent clinical studies have shown that a large number of patients do not respond to ICIs. Moreover, only a few patients achieve a stable and durable response even with combination therapy based on ICIs. Available studies have concluded that the response to immunotherapy and targeted therapy in patients with ccRCC is affected by the tumor immune microenvironment (TIME), which can be manipulated by targeted therapy and tumor genomic characteristics. Therefore, an in-depth understanding of the dynamic nature of the TIME is important for improving the efficacy of immunotherapy or combination therapy in patients with advanced ccRCC. Here, we explore the possible mechanisms by which the TIME affects the efficacy of immunotherapy and targeted therapy, as well as the factors that drive dynamic changes in the TIME in ccRCC, including the immunomodulatory effect of targeted therapy and genomic changes. We also describe the progress on novel therapeutic modalities for advanced ccRCC based on the TIME. Overall, this review provides valuable information on the optimization of combination therapy and development of individualized therapy for advanced ccRCC.

Keywords
clear cell renal cell carcinoma genomic characteristics immunotherapy targeted therapy tumor immune microenvironment
MeSH Terms
Antineoplastic Combined Chemotherapy Protocols/pharmacology,therapeutic use Biomarkers, Tumor/antagonists & inhibitors,genetics Carcinoma, Renal Cell/drug therapy,genetics,immunology,mortality Drug Resistance, Neoplasm/drug effects,genetics Gene Expression Regulation, Neoplastic/drug effects,immunology Humans Immune Checkpoint Inhibitors/pharmacology,therapeutic use Kidney Neoplasms/drug therapy,genetics,immunology,mortality Molecular Targeted Therapy/methods Precision Medicine/methods Progression-Free Survival Randomized Controlled Trials as Topic Tumor Microenvironment/drug effects,genetics,immunology
Chemicals
Biomarkers, Tumor Immune Checkpoint Inhibitors
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Lin Enyu
Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. | Shantou University Medical College, Shantou, China.
Liu Xuechao
Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University, Qingdao, China.
Liu Yanjun
Department of Immunology, School of Basic Medical Science, Southern Medical University, Guangzhou, China.
Zhang Zedan
Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. | Shantou University Medical College, Shantou, China.
Xie Lu
Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Tian Kaiwen
Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Liu Jiumin
Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Yu Yuming
Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Article Info
Journal
Frontiers in immunology
Abbr.
Front Immunol
ISSN
1664-3224
DOI
10.3389/fimmu.2021.653358
Published
2021-00-00
Epub
2021-00-04
Pages
653358
Language
English
Region
Switzerland
NLM ID
101560960
PMCID
PMC7970116
Subset
IM
External Links
PubMed source DOI: 10.3389/fimmu.2021.653358 PMC Full Text View journal details
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