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World J Clin Oncol. Jan 24, 2022; 13(1): 28-38
Published online Jan 24, 2022. doi: 10.5306/wjco.v13.i1.28
Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma
Maja Popovic, Gorana Matovina-Brko, Masa Jovic, Lazar S Popovic
Maja Popovic, Gorana Matovina-Brko, Masa Jovic, Lazar S Popovic, Department of Medical Oncology, Oncology Institute of Vojvodina, University of Novi Sad, Sremska Kamenica 21204, Serbia
Maja Popovic, Lazar S Popovic, Faculty of Medicine, University of Novi Sad, Novi Sad 21000, Serbia
Author contributions: Maja P, Gorana MB, Masa J and Lazar SP designed the research; Maja P, Gorana MB, Masa J and Lazar SP performed the research; Maja P and Lazar SP contributed analytic tools; Maja P, Gorana MB, Masa J and Lazar SP analyzed the data; Maja P wrote the paper.
Conflict-of-interest statement: Authors declare no conflict on interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Lazar S Popovic, MD, PhD, Professor, Department of Medical Oncology, Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Put dr Goldmana 4, Sremska Kamenica 21204, Serbia. lazar.popovic@mf.uns.ac.rs
Received: February 28, 2021
Peer-review started: February 28, 2021
First decision: September 2, 2021
Revised: September 16, 2021
Accepted: December 11, 2021
Article in press: December 11, 2021
Published online: January 24, 2022
Processing time: 327 Days and 19.7 Hours
Abstract

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.

Keywords: Renal cell carcinoma; Immunotherapy; Checkpoint inhibitors; Biomarkers; Tumor microenvironment; Programmed cell death 1 receptor

Core Tip: Renal cell cancer is a highly immunogenic tumor infiltrated by cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved (immunotherapy and immunotherapy/tyrosine kinase inhibitors) as first-line treatment for metastatic clear cell renal cell cancer.