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. 2024 Nov 29;23(1):266.
doi: 10.1186/s12943-024-02176-8.

PD-1/PD-L1 immune checkpoint blockade in breast cancer: research insights and sensitization strategies

Menglei Jin #  1   2 , Jun Fang #  3 , Junwen Peng #  4 , Xintian Wang  5 , Ping Xing  1   2 , Kunpeng Jia  1   2 , Jianming Hu  1   2 , Danting Wang  1   2 , Yuxin Ding  1   2 , Xinyu Wang  3 , Wenlu Li  6 , Zhigang Chen  7   8
Affiliations

PD-1/PD-L1 immune checkpoint blockade in breast cancer: research insights and sensitization strategies

Menglei Jin et al. Mol Cancer. .

Abstract

Immunotherapy targeting programmed cell death-1 (PD-1) and PD-L1 immune checkpoints has reshaped treatment paradigms across several cancers, including breast cancer. Combining PD-1/PD-L1 immune checkpoint blockade (ICB) with chemotherapy has shown promising efficacy in both early and metastatic triple-negative breast cancer, although only a subset of patients experiences durable responses. Identifying responders and optimizing immune drug selection are therefore critical. The effectiveness of PD-1/PD-L1 immunotherapy depends on both tumor-intrinsic factors and the extrinsic cell-cell interactions within the tumor microenvironment (TME). This review systematically summarizes the key findings from clinical trials of ICBs in breast cancer and examines the mechanisms underlying PD-L1 expression regulation. We also highlight recent advances in identifying potential biomarkers for PD-1/PD-L1 therapy and emerging evidence of TME alterations following treatment. Among these, the quantity, immunophenotype, and spatial distribution of tumor-infiltrating lymphocytes stand out as promising biomarkers. Additionally, we explore strategies to enhance the effectiveness of ICBs in breast cancer, aiming to support the development of personalized treatment approaches tailored to the unique characteristics of each patient's tumor.

Keywords: Biomarkers; Breast cancer; Clinical trials; Immune checkpoint blockade; PD-1/PD-L1; Sensitization strategies.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: No datasets were generated or analysed during the current study. Consent for publication: All authors consent to publication. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Search results clinical trials in breast cancer for anti-PD-1/PD-L1. a–c show the histogram of clinical trials number in breast cancer since 2010, by trial phase (a), by trial setting (b), and by subtype (c). d-e show the number of anti-PD-1/PD-L1 clinical trials in breast cancer per year by starting date
Fig. 2
Fig. 2
The Regulatory Mechanism of PD-L1 Expression. The complicated regulation of PD-L1 expression includes various transcription factors, epigenetic and genetic alterations. ERO1α, endoplasmic reticulum oxidoreductase; IFN-γ, Interferon-γ; IL-6, Interleukin-6; JAK, Janus Kinase; EGF, Epidermal growth factor; GSK3β, Glycogen synthase kinase 3β; B3GNT3, β-1,3-N-acetylglucosaminyltransferase 3; PMA, phorbol 12-myristate 13-acetate; PI3K, Phosphatidylinositide 3-kinases; HIF1α, hypoxia-inducible factor 1α; STAT, signal transducer and activator of transcription; TCF, T cell-specific transcription factor; LEF, lymphoid enhancer-binding factor; NF-κB, nuclear factor κB; AP1, activator protein 1; H3K4me3, histone H3 lysine 4 trimethylation; miRNA, microRNAs
Fig. 3
Fig. 3
Tumor microenvironment and variation of associated immune cells after immunotherapy in breast cancer. DC, dendritic cell; TAM, tumor-associated macrophage; IL, Interleukin
Fig. 4
Fig. 4
An overview of biomarkers for immunotherapy response in breast cancer. TMB, tumor mutational burden; TME, tumor microenvironment; CNA, copy number alterations; dMMR, defects in mismatch repair; MSI, microsatellite instability; POLE, polymerase epsilon; mSAF, maximum somatic allele frequency
Fig. 5
Fig. 5
Summary of combination therapy strategies for sensitization with PD-1/PD-L1 immune checkpoint blockade for breast cancer therapy
See this image and copyright information in PMC

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