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

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Mar 22

PMID 33746989

Citations 18

Authors

Enyu Lin

Xuechao Liu

Yanjun Liu

Zedan Zhang

Lu Xie

Kaiwen Tian

Jiumin Liu

Yuming Yu

Affiliations

Soon will be listed here.

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.

Citing Articles

Identifying an Inversin as a Novel Prognostic Marker in Patients with Clear-Cell Renal Cell Carcinoma.

Urlic I, Soljic V, Vukoja M, Marijanovic I, Kraljevic M, Urlic M Int J Mol Sci. 2024; 25(22).

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Developing hypoxia and lactate metabolism-related molecular subtypes and prognostic signature for clear cell renal cell carcinoma through integrating machine learning.

Liu J, Yang T, Liu J, Hao X, Guo Y, Luo S Discov Oncol. 2024; 15(1):653.

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PMID: 38854736 PMC: 11162108. DOI: 10.3389/fonc.2024.1391464.

The Role of the Complement in Clear Cell Renal Carcinoma (ccRCC)-What Future Prospects Are There for Its Use in Clinical Practice?.

Panebianco M, Ciccarese C, Strusi A, Beccia V, Carbone C, Agostini A Cancers (Basel). 2024; 16(3).

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Primary and acquired resistance to first-line therapy for clear cell renal cell carcinoma.

Astore S, Baciarello G, Cerbone L, Calabro F Cancer Drug Resist. 2023; 6(3):517-546.

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References

Norian L, Rodriguez P, OMara L, Zabaleta J, Ochoa A, Cella M . Tumor-infiltrating regulatory dendritic cells inhibit CD8+ T cell function via L-arginine metabolism. Cancer Res. 2009; 69(7):3086-94. PMC: 2848068. DOI: 10.1158/0008-5472.CAN-08-2826. View

Bentebibel S, Hurwitz M, Bernatchez C, Haymaker C, Hudgens C, Kluger H . A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors. Cancer Discov. 2019; 9(6):711-721. DOI: 10.1158/2159-8290.CD-18-1495. View

Riabov V, Gudima A, Wang N, Mickley A, Orekhov A, Kzhyshkowska J . Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis. Front Physiol. 2014; 5:75. PMC: 3942647. DOI: 10.3389/fphys.2014.00075. View

Fukumura D, Kloepper J, Amoozgar Z, Duda D, Jain R . Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol. 2018; 15(5):325-340. PMC: 5921900. DOI: 10.1038/nrclinonc.2018.29. View

Klempner S, Fabrizio D, Bane S, Reinhart M, Peoples T, Ali S . Tumor Mutational Burden as a Predictive Biomarker for Response to Immune Checkpoint Inhibitors: A Review of Current Evidence. Oncologist. 2019; 25(1):e147-e159. PMC: 6964127. DOI: 10.1634/theoncologist.2019-0244. View

Pan D, Kobayashi A, Jiang P, Ferrari de Andrade L, Tay R, Luoma A . A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing. Science. 2018; 359(6377):770-775. PMC: 5953516. DOI: 10.1126/science.aao1710. View

Charych D, Hoch U, Langowski J, Lee S, Addepalli M, Kirk P . NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models. Clin Cancer Res. 2016; 22(3):680-90. DOI: 10.1158/1078-0432.CCR-15-1631. View

Hara T, Miyake H, Fujisawa M . Expression pattern of immune checkpoint-associated molecules in radical nephrectomy specimens as a prognosticator in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. Urol Oncol. 2017; 35(6):363-369. DOI: 10.1016/j.urolonc.2017.01.002. View

Maxwell P, Wiesener M, Chang G, Clifford S, Vaux E, Cockman M . The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature. 1999; 399(6733):271-5. DOI: 10.1038/20459. View

10.

Voronov E, Carmi Y, Apte R . The role IL-1 in tumor-mediated angiogenesis. Front Physiol. 2014; 5:114. PMC: 3975103. DOI: 10.3389/fphys.2014.00114. View

11.

Motzer R, Escudier B, Mcdermott D, George S, Hammers H, Srinivas S . Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015; 373(19):1803-13. PMC: 5719487. DOI: 10.1056/NEJMoa1510665. View

12.

Huang Y, Yuan J, Righi E, Kamoun W, Ancukiewicz M, Nezivar J . Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc Natl Acad Sci U S A. 2012; 109(43):17561-6. PMC: 3491458. DOI: 10.1073/pnas.1215397109. View

13.

Macdonald A . Use of mTOR inhibitors in human organ transplantation. Expert Rev Clin Immunol. 2010; 3(3):423-36. DOI: 10.1586/1744666X.3.3.423. View

14.

Motzer R, Hutson T, Cella D, Reeves J, Hawkins R, Guo J . Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013; 369(8):722-31. DOI: 10.1056/NEJMoa1303989. View

15.

Walter S, Weinschenk T, Stenzl A, Zdrojowy R, Pluzanska A, Szczylik C . Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med. 2012; 18(8):1254-61. DOI: 10.1038/nm.2883. View

16.

Ying H, Elpek K, Vinjamoori A, Zimmerman S, Chu G, Yan H . PTEN is a major tumor suppressor in pancreatic ductal adenocarcinoma and regulates an NF-κB-cytokine network. Cancer Discov. 2011; 1(2):158-69. PMC: 3186945. DOI: 10.1158/2159-8290.CD-11-0031. View

17.

Li Y, Zhao H, Ren X . Relationship of VEGF/VEGFR with immune and cancer cells: staggering or forward?. Cancer Biol Med. 2016; 13(2):206-14. PMC: 4944543. DOI: 10.20892/j.issn.2095-3941.2015.0070. View

18.

Vetsika E, Koukos A, Kotsakis A . Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer. Cells. 2019; 8(12). PMC: 6953061. DOI: 10.3390/cells8121647. View

19.

Miao D, Margolis C, Gao W, Voss M, Li W, Martini D . Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science. 2018; 359(6377):801-806. PMC: 6035749. DOI: 10.1126/science.aan5951. View

20.

Najjar Y, Rayman P, Jia X, Pavicic Jr P, Rini B, Tannenbaum C . Myeloid-Derived Suppressor Cell Subset Accumulation in Renal Cell Carcinoma Parenchyma Is Associated with Intratumoral Expression of IL1β, IL8, CXCL5, and Mip-1α. Clin Cancer Res. 2016; 23(9):2346-2355. PMC: 5411325. DOI: 10.1158/1078-0432.CCR-15-1823. View