The role of myeloid-derived suppressor cells in lung cancer and targeted immunotherapies

ABSTRACT

Introduction

Lung cancer is the deadliest cancer in both sexes combined globally due to significant delays in diagnosis and poor survival. Despite advances in the treatment of lung cancer, the overall outcomes remain poor and traditional chemotherapy fails to provide long-term benefits for many patients. Therefore, new treatment strategies are needed to increase overall survival. Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells taking part in lung cancer, as has been described in other types of tumors. MDSCs immunosuppressive activity is mediated by arginases (ARG-1 and ARG–2), nitric oxide (NO), reactive oxygen species (ROS), peroxynitrite, PD-1/PD-L1 axis, and different cytokines. MDSCs can be a target for lung cancer immunotherapy by inducing their differentiation into mature myeloid cells, elimination, attenuation of their function, and inhibition of their accumulation.

Areas covered

In this review, the immunosuppressive function of MDSCs, their role in lung cancer, and strategies to target them, which could result in increased efficacy of immunotherapy in patients with lung cancer, are discussed.

Expert opinion

Identification of important mechanisms and upstream pathways involved in MDSCs functions paves the way for further preclinical and clinical lung cancer research, which could lead to the development of novel therapeutic approaches.

KEYWORDS:

• NSCLC
• lung cancer
• MDSCs
• immunotherapy
• immunosuppression
• anticancer

Article highlights

• Despite significant progress in lung cancer treatment, it remains as an important cause of cancer-related death worldwide.

• MDSCs are diverse cells derived from immature myeloid cells (IMCs) in pathological conditions, such as cancer.

• MDSCs play a crucial role in suppressing the immune system and promoting tumors' growth, angiogenesis, and metastasis.

• Different factors mediate MDSCs recruitment and immunosuppressive functions, which can be studied as a new strategy for targeted lung cancer immunotherapy.

• Further in-depth studies about MDSCs targeting alone/in combination with chemo- and/or immunotherapies are needed.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has received research funding to their institution from: Bristol Myers Squibb, Merck, Palobiofarma and Genentech. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper received no funding.