Targeting Immune-Mediated Suppressive Mechanisms as a Cancer Immunotherapy Strategy

Mahima Larals*

Department of Microbiology, NMCRC for Medical Education Technologies, Pune, India

Corresponding Author:
Mahima Larals
Department of Microbiology
NMCRC for Medical Education Technologies, Pune, India
E-mail: mahimalarals@gmail.com

Received Date: November 05, 2021; Accepted Date: November 22, 2021; Published Date: November 30, 2021

Citation: Larals M (2021) Targeting Immune-Mediated Suppressive Mechanisms as a Novel Cancer Immunotherapy Strategy. J Med Microbiol Immunol Res Vol.4 No.2:22

Copyright: © 2021 Larals M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Introduction

Over the last decade, new types of cancer treatments, generally known as cancer immunotherapies, have developed and shown amazing outcomes, but only in a small percentage of cancer patients. Immunotherapies stimulate or restore effective antitumor immune responses by mobilizing the immune system. Immune Checkpoint Inhibitors (ICIs) that target the CTLA-4/B7 and PD1/PDL1 immune checkpoints (so-called ICIs) are currently widely used in clinical trials. Although ICIs frequently provide long-term benefits, full or virtually complete tumor responses are rare, and resistance is shown in a significant proportion of patients. Primary or acquired resistance to ICIs is widespread, and identifying predictive indicators of effectiveness or resistance is challenging. The search for new alternative or complementary targets that activate, release, or augment anticancer immune responses is presently in full swing. ICIs fine-tune the immune response and control hyperactivation by acting as negative regulators of T cell activation that have evolved through time [1]. The most powerful T cell immunological checkpoint molecules are Cytotoxic T Lymphocyte Antigen 4 (CTLA4) and Programmed Cell Death 1 (PD1). They have biological effects in different parts of the body and at different periods during the T cell's lifetime. As a result, they functionally complement each other, ensuring that T cell responses maintain self-tolerance while successfully defending the body against infections and neoplasia. Several pioneering research groups have successfully targeted CTLA4 and PD1 astherapiesfor a range ofrefractory malignancies. In this context, developing strategies to target the immunosuppressive Tumor Micro Environment (TME) is of utmost importance. The current challenges are to identify the immunosuppressive mechanisms that most significantly contribute to cancer cells' primary or acquired resistance to antitumor immune responses at the molecular and cellular levels, as well as to demonstrate that targeting these mechanisms has therapeutic anti-tumor activity. To create innovative ways to enhance the result and raise the proportion of patientsresponding to cancer immunotherapy, a deeper knowledge of the interaction between cancer cells and immune cells is necessary. Regulatory T cells (Tregs), for example, are well-known to promote local immunosuppression within tumors. They are key modulators of adaptive immunity and are required to maintain self-tolerance. Because of the variety of immunosuppressive mechanisms used by these cells to carry out their functions, the number of different Treg subpopulations identified to date, and the existence of many other cell types endowed with immunosuppressive functions, new research is needed to identify and better define novel therapeutic targets that could aid in the development of effective anti-tumor immunity. The goal ofthisissue wasto give a view ofthe immunosuppressive mechanismsthat appeartopredominatewithintheTME, aswell as to identify novel, therapeutically targetable immunosuppressive processes. The different articles demonstrate how far the discipline has progressed while also emphasizing its intricacy [2].

Despite great success in cancer immunotherapy, immune checkpoint-targeting drugs are not the most popular weapon in the armory of cancer therapy. Accumulating evidence suggests that the tumor immune microenvironment plays a critical role in anti-cancer immunity, which may result in immune checkpoint blockade therapy being ineffective, in addition to other novel immunotherapies in cancer patients. In the present review, we discuss the deficiencies of current cancer immunotherapies. More importantly, we highlight the critical role of tumor immune microenvironment regulators in tumor immune surveillance, immunological evasion, and the potential for their further translation into clinical practice. Based on their general targetability in clinical therapy, we believe that tumor immune microenvironment regulators are promising cancer immunotherapeutic targets. Targeting the tumor immune microenvironment, alone or in combination with immune checkpoint-targeting drugs, might benefit cancer patients in the future.

To date, immune checkpoint (ICP)-targeting drugs, such as anticytotoxic T-lymphocyte-associated protein 4 (CTLA-4), antiprogrammed cell death protein 1 (PD-1), and anti-PD-1 ligand 1 (PD-L1), have displayed considerable success in a number of cancer immunotherapies, including melanoma, lung cancer, and other commonly diagnosed cancers. Accordingly, ICP blockadebased therapeutic strategies have been championed in cancer research and therapy, often in the name of patient benefit. Currently, for patients with advanced head and neck squamous cell carcinoma, non-small cell lung cancer (NSCLC, squamous and non-squamous carcinoma), melanoma, urothelial and kidney cancers, Merkel cell carcinoma, refractory Hodgkin lymphoma, microsatellite instability-high colorectal cancer, gastric cancer, and hepatocellular carcinoma, therapeutic ICP blockade has become a part of the standard of care. Clinical trials have been initiated to investigate their efficacy for the treatment of additional malignant diseases [3]. However, increasing numbers of studies have shown that the positive response rate among patients receiving immune checkpoint-targeting drugs remains quite low, an issue that remains to be solved. Previous studies have demonstrated that in the majority of the cases, clinical benefit is commonly prevented by acquired resistance to the tumor and primary tumor refractoriness to the ICP-targeting drugs. Furthermore, clinical decisions to use these drugs, especially dual CTLA-4 and PD-1 blockade, should consider their potential to induce high-grade immune-related adverse events. Thus, the clinical practice of checkpoint-targeting therapy remains problematic.

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