Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment

Sep 24, 2026

Checkpoint proteins regulate immune activity and tumors exploit them to avoid immune recognition and uncontrolled growth. Immune checkpoint inhibitors block key checkpoint targets, enabling immune restoration to attack cancer cells and restrain tumor progression. Clinical findings are supported by clinical trial evidence and multiple FDA-approved agents covering melanoma and other cancer types. These therapies act mainly on CTLA-4 and PD-1/PD-L1 pathways, can be used alone or with surgery, radiation, or chemotherapy, and generally show fewer side effects than conventional chemotherapy, though fatigue, rash, fever, and rare serious toxicities may occur.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

Tumor immune microenvironment and immune checkpoints

Mechanisms of immune evasion and resistance

Review Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment Norah A. Alturki Citation: Alturki, N.A. Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment. J. Clin. Med. 2023, 12, 4301. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/jcm12134301](10.3390/jcm12134301) Academic Editor: Arutselvan Natarajan Received: 3 May 2023 Revised: 14 June 2023 Accepted: 21 June 2023 Published: 27 June 2023 Copyright: © 2023 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . Clinical Laboratory Science Department, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia; [noalturki@ksu.edu.sa](noalturki@ksu.edu.sa) Abstract: Checkpoint proteins are an integral part of the immune system and are used by the tumor cells to evade immune response, which helps them grow uncontrollably. By blocking these proteins, immune checkpoint inhibitors can restore the capability of the immune system to attack cancer cells and stop their growth. These ﬁndings are backed by adequate clinical trial data and presently, several FDA-approved immune checkpoint inhibitors exist in the market for treating various types of cancers, including melanoma, hepatocellular, endometrial, lung, kidney and others. Their mode of action is inhibition by targeting the checkpoint proteins CTLA-4, PD-1, PD-L1, etc. They can be used alone as well as in amalgamation with other cancer treatments, like surgery, radiation or chemotherapy. Since these drugs target only speciﬁc immune system proteins, their side effects are reduced in comparison with the traditional chemotherapy drugs, but may still cause a few affects like fatigue, skin rashes, and fever. In rare cases, these inhibitors are known to have caused more serious side effects, such as cardiotoxicity, and inﬂammation in the intestines or lungs. Herein, we provide an overview of these inhibitors and their role as biomarkers, immune-related adverse outcomes and clinical studies in the treatment of various cancers, as well as present some future perspectives. Keywords: immune checkpoint inhibitors; PD-1; PD-L1; CTLA-4; cancer treatment; neoantigens 1. Introduction Microenvironment of the tumor is monitored and regulated by immune surveillance through innate and adaptive immune systems [1] . Antigen-presenting cells have a fundamental role in this surveillance, as they identify and present tumor neoantigens to naive T-cells [2] . When exposed to the antigen, naive T-cells multiply and become activated to initiate an anti-tumor immune response [3] . This reaction is controlled by both stimulatory and inhibitory signaling molecules [4,5] . The inhibitory signals are mediated through immune checkpoints, such as B and T lymphocyte attenuator (BTLA), programmed death protein 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4) [6,7] . CTLA-4 and PD-1 exist on the exterior of T-cells and can stop their activation [8] . CTLA-4 is also found on Treg cells, and aids in immune suppression. PD-1 is also found on the exterior of B and other immune response cells [9] . When PD-1 binds to its partner proteins, it can also stop the T-cell response [8] . However, cancer cells within the tumor microenvironment can escape the anti-tumor inﬂuences by stimulating these checkpoints through CTLA4 or PD-1/PD-L1 expression enhancement. They also attempt this by suppressing antigen presentation [10,11] . Overexpression of these checkpoints on immune cellular surface can limit the capacity of the immune system to identify and attack cancerous cells. This permits the cancer cells to escape scrutiny and grow uncontrollably [12,13] . This is

FAQs

What is the role of immune checkpoint proteins in cancer?

Checkpoint proteins are part of the immune system, but tumor cells can use them to evade immune responses, helping cancer grow uncontrollably.

How do immune checkpoint inhibitors improve cancer treatment?

They block checkpoint proteins such as CTLA-4 and PD-1/PD-L1, restoring the immune system’s ability to attack cancer cells and stop tumor growth.

What treatment options can be combined with immune checkpoint inhibitors?

Immune checkpoint inhibitors can be used alone or combined with surgery, radiation, or chemotherapy.

Sep 24, 2026

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