PD-1/PD-L1 blockade in HIV-associated advanced lung cancer - from mechanisms to clinical practice

Sep 23, 2026

Uploaded by Theodore

Antiretroviral therapy has extended survival for people living with HIV, yet this has coincided with a growing burden of non-AIDS-defining malignancies, especially advanced non-small cell lung cancer. Targeted PD-1 pathway and PD-L1 ligand inhibitors are now central to modern immunotherapy, but their use in HIV-positive patients with concurrent lung cancer remains underexplored. This review details how PD-1/PD-L1 blockade can enhance tumor immunity while also reversing latent HIV and restoring immune function, supported by evidence of favorable safety and promising efficacy in ART-controlled patients. Further large, well-designed trials are required to confirm long-term outcomes amid study limitations such as small samples and heterogeneity.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

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Introduction

PD-1 and PD-L1 roles in immune regulation

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TYPE Review PUBLISHED 10 February 2026 DOI 10.3389/fimmu.2026.1708278 OPEN ACCESS EDITED BY Sheefa Mirza, University of Witwatersrand, South Africa REVIEWED BY Aabid Hussain, Cleveland Clinic, United States Niel De Beer, University of Pretoria, South Africa *CORRESPONDENCE Haicheng Tang [tanghaicheng@shaphc.org](tanghaicheng@shaphc.org)[ ](tanghaicheng@shaphc.org)Qingguo Wu [wuqingguo@shaphc.org](wuqingguo@shaphc.org) †These authors have contributed equally to this work RECEIVED 26 September 2025 REVISED 21 January 2026 ACCEPTED 26 January 2026 PUBLISHED 10 February 2026 CITATION Chen R, Ren S, Tang H and Wu Q (2026) PD-1/PD-L1 blockade in HIV-associated advanced lung cancer: from mechanisms to clinical practice. Front. Immunol. 17:1708278 . doi: 10.3389/fimmu.2026.1708278 COPYRIGHT © 2026 Chen, Ren, Tang and Wu. This isan 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/PD-L1 blockade in HIVassociated advanced lung cancer: from mechanisms to clinical practice Ruifang Chen †, Shuai Ren †, Haicheng Tang* and Qingguo Wu* Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center, Shanghai, China The advent of antiretroviral therapy (ART) has ushered in a remarkable era of prolonged survival for individuals living with Human Immunodeﬁciency Virus (HIV) . Yet this prolonged survival has paradoxically coincided with an increasing burden of non-AIDS-deﬁning malignancies, particularly advanced non-small cell lung cancer. Targeted inhibitors of the programmed cell death protein-1 (PD-1) pathway and its ligand, programmed death-ligand 1 (PD-L1), have now become the cornerstone of modern immunotherapy. Nevertheless, comprehensive studies evaluating the application of these inhibitors in HIV-positive individuals with concurrent lung cancer remain scarce. This review elucidates the dual mechanism of action of PD-1/PD-L1 inhibitors in this patient population: on one hand, blockade of the PD-1/PD-L1 axis enhances anti-tumor activity in vivo, while on the other, it reverses latent HIV infection and restores immune function. Current evidence suggests that PD-1/PD-L1 inhibitors demonstrate favorable safety and promising efﬁcacy in ART-controlled HIV patients with lung cancer. However, comprehensive clinical trials remain imperative to validate their longterm outcomes, given the existing limitations of small sample sizes and population heterogeneity in current studies. This article seeks to establish a theoretical foundation for tailoring immunotherapy strategies to this unique patient population. KEYWORDS HIV, immunotherapy, lung cancer, PD-1 inhibitor, PD-L1 inhibitor 1 Introduction Programmed cell death protein 1 (PD-1, CD279) is expressed on activated immune cells, including T cells, B lymphocytes, NK cells, macrophages, dendritic cells, and monocytes, with particularly high expression observed in tumor-inﬁltrating T cells (1) . Programmed Cell Death Ligand 1 (PD-L1, also termed CD274 or B7-H1) is a key ligand of PD-1, primarily expressed on antigen-presenting cells and tumor cell surfaces (2) . Under physiological conditions, the PD-1/PD-L1 interaction delivers inhibitory signals that suppress T-cell activation, cytokine production, and cytotoxic function. This regulatory mechanism promotes immune tolerance by attenuating CD8+ T-cell survival and effector responses (3). Among all immune cells, T cells serve as the most potent effectors in directly eliminating cancer cells. Upon activation by antigen stimulation, the immune system concurrently initiates a

FAQs

What is the main purpose of PD-1/PD-L1 blockade in this review?

To explain how PD-1/PD-L1 inhibitors act in HIV-associated advanced lung cancer, covering both anti-tumor effects and immune restoration in HIV-positive patients.

How does PD-1/PD-L1 signaling contribute to cancer immune evasion?

PD-1/PD-L1 interaction delivers inhibitory signals that suppress T-cell activation, cytotoxic function, and anti-tumor immune responses, allowing tumors to avoid immune killing.

What evidence does the review indicate about safety and efficacy in ART-controlled patients?

Current evidence suggests favorable safety and promising efficacy of PD-1/PD-L1 inhibitors in ART-controlled HIV patients with lung cancer.

Why are further clinical trials still necessary?

Comprehensive trials are needed to validate long-term outcomes, because existing studies face limitations such as small sample sizes and population heterogeneity.

Sep 23, 2026

Uploaded by Theodore