PD-1/PD-L1

Overview

The PD-1/PD-L1 pathway is a critical immune checkpoint mechanism that plays a significant role in regulating the immune response, particularly in the context of cancer. Programmed cell death protein 1 (PD-1) is an inhibitory receptor expressed on activated T-lymphocytes, while Programmed Death-Ligand 1 (PD-L1) is its ligand, predominantly found on tumor cells and antigen-presenting cells. The interaction between PD-1 and PD-L1 inhibits T-cell activation and proliferation, allowing tumors to evade immune surveillance. This pathway has become a focal point in cancer immunotherapy, with immune checkpoint inhibitors targeting PD-1 and PD-L1 demonstrating improved survival rates in various malignancies.

Focus of Latest Publications

Recent studies have highlighted the significance of the PD-1/PD-L1 axis in cancer treatment and the ongoing challenges in predicting patient responses to immunotherapy. For instance, a study published in Gut Microbes (PMID: 42026803) emphasized the need for predictive biomarkers to enhance the efficacy of immune checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4, as variability in patient responses remains a significant hurdle. Similarly, research in Clinical and Experimental Pharmacology & Physiology (PMID: 42203488) identified that Aurora A-mediated T-lymphocyte apoptosis compromises PD-1/PD-L1-mediated immune responses, suggesting a molecular basis for resistance to immunotherapy in non-small cell lung cancer (NSCLC) patients with high Aurora A expression.

In the context of breast cancer, a study in Analytical Chemistry (PMID: 42065221) noted that the PD-1/PD-L1 blockade is a cornerstone of immunotherapy, yet the scarcity of predictive biomarkers limits its clinical benefits. Another investigation in Nature Microbiology (PMID: 41998161) demonstrated that Faecalibacterium prausnitzii can reprogram PD-L1 trafficking, sensitizing colorectal cancer to immunotherapy, which underscores the potential for microbiome interactions to influence PD-1/PD-L1 dynamics.

Moreover, studies have explored novel therapeutic strategies, such as bispecific antibodies targeting both PD-L1 and tumor-associated antigens (PMID: 41951084), and the combination of PD-1 inhibitors with cytotoxic chemotherapy in advanced biliary tract cancer (PMID: 42026958). These approaches aim to enhance immune activation and overcome resistance mechanisms associated with PD-1/PD-L1 interactions.

Research has also focused on the molecular underpinnings of PD-L1 expression and its implications for treatment. For example, a study in Cancer Letters (PMID: 41690450) revealed that metformin can suppress PD-L1 expression through SLC5A11-dependent pathways, thereby enhancing the efficacy of cancer immunotherapy. Additionally, the identification of age-associated genomic alterations and PD-L1 expression in pulmonary ground-glass opacities (PMID: 42068110) highlights the importance of understanding patient-specific factors in tailoring immunotherapy.

Key Publications

• Jun Aurora A-Mediated Exosomal Secretion of miR-644a Promotes T-Lymphocyte Apoptosis Through the NOXA/p4E-BP1/MCL-1 Pathway. (Clinical and experimental pharmacology & physiology, 2026, PMID 42203488): "Aurora A-driven T-lymphocyte apoptosis via the NOXA-MCL-1 axis compromises PD-1/PD-L1-mediated immune responses, providing a molecular rationale for immunotherapy resistance in Aurora A-high NSCLC patients."
• May Flexible Dual-Apt Scaffolds Reveal gPD-L1-sEVs in Breast Cancer. (Analytical chemistry, 2026, PMID 42065221): "The PD-1/PD-L1 blockade is a cornerstone of breast cancer immunotherapy, yet predictive biomarkers for immunotherapy outcomes remain scarce, restricting its clinical benefit."
• May Age-Associated Targetable Genomic Alterations and PD-L1 Expression in 2509 Patients With Pulmonary Ground-Glass Opacities. (Cancer medicine, 2026, PMID 42068110): "To investigate the landscape of targetable genomic alterations and programmed cell death ligand 1 (PD-L1) expression in pulmonary ground-glass opacities (GGOs) and their association with age."
• May A rationally designed bispecific antibody targeting GPC3 and PD-L1 induces tumor-directed immune activation and cytotoxicity. (International journal of biological macromolecules, 2026, PMID 41951084): "to selectively target tumor cells co-expressing hepatocellular carcinoma-associated antigen glypian-3 (GPC3) and programmed Cell Death Ligand 1 (PD-L1)."
• May Gilteritinib overcomes second‑generation TKIs resistance in ALK‑rearranged non‑small‑cell lung cancer by inhibiting PD‑L1 and CD8 co‑expression. (International journal of molecular medicine, 2026, PMID 42059267): "Western blotting, reverse transcription-quantitative PCR and immunofluorescence were used to examine programmed death-ligand 1 (PD-L1) and cluster of differentiation 8 (CD8) expression."
• Apr Smart MnO2 Nanosheet-Copper Carbon Dot Nanoplatform Enabling Multimodal Therapy to Reverse Hypoxia and Reprogram the Tumor Immune Microenvironment. (ACS applied materials & interfaces, 2026, PMID 41873798): "thus significantly downregulating the expressions of HIF-1α and PD-L1."
• Apr Tumor DNA methylation subtypes predict immunotherapy outcomes in pleural mesothelioma patients in the NIBIT-EPI-MESO study. (Nature genetics, 2026, PMID 42045690): "standard therapy with immune checkpoint inhibitors (ICIs) CTLA-4 and PD-1 is still clinically unsatisfying."
• Apr CCR4 expression defines a targetable subset of T-cell acute lymphoblastic leukemia. (Blood advances, 2026, PMID 41671457): "We analyzed the T-ALL microenvironment from 40 patients treated on the AALL0434 clinical trial and identified a subpopulation of bone marrow-enriched CCR4+ FOXP3+ T-regulatory cells that express immune checkpoints (PD-1 and TIGIT) and could be targeted with anti-CCR4 therapy."
• Apr SLC5A11 mediates metformin-induced PD-L1 suppression to enhance cancer immunotherapy through AMPK-IRF1 signaling. (Cancer letters, 2026, PMID 41690450): "Metformin suppressed PD-L1 expression across multiple cancer models through SLC5A11-dependent activation of AMPK and subsequent JAK2-STAT1-IRF1 downregulation."
• Apr Targeting PD-1+ T cells with chimeric antigen receptors to reduce the HIV reservoir. (Science advances, 2026, PMID 42030390): "Here, we investigated the possibility of redirecting CAR-T cells against a cellular biomarker of the HIV reservoir, the programmed cell death protein 1 (PD-1)."