IL-2 in combination with immune checkpoints inhibitors as a promising approach for cancer immunotherapy: A literature review

Abstract

Relevance: Interleukin-2 (IL-2) alone has been shown to induce tumor regression and approved to treat metastatic renal cancer and melanoma. Checkpoint inhibitors realize their therapeutic effect through stimulation of immune system effectors. One of such mechanisms is the enhancement of IL-2 production by T-helpers.
 The purpose of the study was to determine the effectiveness of IL-2 administration as a component of combined immunotherapy with immune checkpoint inhibitors and to suggest the mechanisms by which IL-2 can reduce the frequency and severity of side effects during checkpoint inhibitor therapy without reducing their effectiveness.
 Methods: The literature search was performed in the PubMed, SCOPUS, and Web of Science databases by the keywords in article titles: “immunotherapy,” “checkpoint inhibitors,” “interleukin-2,” and “combination therapy” for the period 2011-2021.
 A total of 248 relevant articles were found. The review’s inclusion criteria were: clinical cases; data of clinical research methods; data on humans/body fluids from humans; literature reviews and meta-analyses. The selected 24 articles met the search criteria and were included in the study.
 Results: The combined action of IL-2 and сheckpoint inhibitors increases the proliferative and killer activity of the antitumor immunity effectors compared to the action of the same drugs in mono-mode at a level exceeding the summation effect.
 Conclusion: The combination of IL-2 and сheckpoint inhibitors can increase the effectiveness of anticancer treatment and is a promising area of immunotherapy