PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment

Sep 24, 2026

PD-1 (programmed cell death protein-1) and PD-L1 (programmed cell death ligand-1) are central regulators of immune activity, helping maintain tolerance and preventing autoimmunity. Cancer cells hijack this control to evade immune surveillance and support tumor growth. Targeting the PD-1/PD-L1 axis has reshaped cancer therapy, showing strong effectiveness across multiple cancer types. The review examines PD-1 structure and signaling, PD-1/PD-L1 inhibitors, clinical resistance, and treatment challenges, including emerging combination strategies with chemotherapy, radiation, and surgery.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

PD-1/PD-L1 role in immune regulation

Cancer immune evasion and checkpoint upregulation

PD-1/PD-L1–targeted therapies and clinical impact

Resistance and treatment challenges

Combination approaches in immunotherapy

TYPE Review PUBLISHED 01 December 2023 DOI 10.3389/fimmu.2023.1296341 OPEN ACCESS EDITED BY Jesse Haramati, University of Guadalajara, Mexico REVIEWED BY Jieying Zhang, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, China Hao Chi, Southwest Medical University, China Adeleye Oluwatosin Adeshakin, St. Jude Children ’s Research Hospital, United States *CORRESPONDENCE Kamal A. Qureshi [ka.qurishe@qu.edu.sa](ka.qurishe@qu.edu.sa)[ ](ka.qurishe@qu.edu.sa)Humaira Farooqi [hfarooqi@jamiahamdard.ac.in](hfarooqi@jamiahamdard.ac.in)[ ](hfarooqi@jamiahamdard.ac.in)Ashok Aspatwar ashok.aspatwar@tuni. ﬁ RECEIVED 18 September 2023 ACCEPTED 08 November 2023 PUBLISHED 01 December 2023 CITATION Parvez A, Choudhary F, Mudgal P, Khan R, Qureshi KA, Farooqi H and Aspatwar A (2023) PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment. Front. Immunol. 14:1296341 . doi: 10.3389/fimmu.2023.1296341 COPYRIGHT © 2023 Parvez, Choudhary, Mudgal, Khan, Qureshi, Farooqi and Aspatwar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughsin cancer treatment Adil Parvez 1, Furqan Choudhary 1, Priyal Mudgal 1, Rahila Khan 1, Kamal A. Qureshi 2*, Humaira Farooqi 1* and Ashok Aspatwar 3* 1 Department of Biotechnology, School of Chemical and Life Sciences, Jamia, Hamdard, New Delhi, India, 2 Department of Pharmaceutics, Unaizah College of Pharmacy, Qassim University, Unaizah, Qassim, Saudi Arabia, 3 Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland PD-1 (Programmed Cell Death Protein-1) and PD-L1 (Programmed Cell Death Ligand-1) play a crucial role in regulating the immune system and preventing autoimmunity. Cancer cells can manipulate this system, allowing them to escape immune detection and promote tumor growth. Therapies targeting the PD-1/ PD-L1 pathway have transformed cancer treatment and have demonstrated signiﬁcant effectiveness against various cancer types. This study delves into the structure and signaling dynamics of PD-1 and its ligands PD-L1/PD-L2, the diverse PD-1/PD-L1 inhibitors and their efﬁcacy, and the resistance observed in some patients. Furthermore, this study explored the challenges associated with the PD-1/PD-L1 inhibitor treatment approach. Recent advancements in the combination of immunotherapy with chemotherapy, radiation, and surgical procedures to enhance patient outcomes have also been highlighted. Overall, this study offers an in-depth overview of the signiﬁcance of PD-1/PD-L1 in cancer immunotherapy and its future implications in oncology. KEYWORDS PD-1, PD-L1, cancer immunotherapy, immune checkpoint inhibitors, combination therapy, monoclonal antibody Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) Parvez et al. 10.3389/fimmu.2023.1296341 GRAPHICAL ABSTRACT 1 Introduction Cancer is a signiﬁcant public health concern that contributes to global mortality and morbidity rates. In 2020, it was reported that there were approximately 18.1 million new cases of cancer worldwide, excluding non-melanoma skin cancer, with 8.8 million (48%) in females and 9 .3 million (52%) in males. This resulted in a ratio of 10 males to every 9.5 females. The global agestandardized incidence rate was 178.1 per 100,000 females and 206.9 per 100,000 males. The four most common types of cancer worldwide are breast, lung, bowel (including anus), and prostate cancers, which collectively account for 43% of all n

FAQs

What is the role of PD-1 and PD-L1 in the immune system?

PD-1 and PD-L1 regulate immune activity and help prevent autoimmunity by controlling anti-tumor immune responses. They are also involved in the immune system’s monitoring of abnormal cells.

How do cancer cells use the PD-1/PD-L1 pathway to their advantage?

Cancer cells manipulate the PD-1/PD-L1 control system to avoid immune detection. This supports tumor growth by promoting immune escape.

What topics does the review cover regarding PD-1/PD-L1 therapies?

The review covers PD-1 structure and signaling, PD-1/PD-L1 inhibitors and their efficacy, resistance observed in some patients, and challenges with this treatment approach, including recent combination strategies.

Sep 24, 2026

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