Expanding indications of immune checkpoint inhibitors: a decade of success going strong.

Harnessing immunity against breast cancer: from checkpoints to cell therapies

Breast cancer (BC) remains the leading cause of cancer-related mortality and a major contributor to disease burden among women worldwide. Although PD‑1/PD‑L1‑targeting immune checkpoint inhibitors have become a standard treatment for certain triple‑negative breast cancer subgroups, their use across the broader BC population is limited by intrinsic resistance, an immunosuppressive tumor microenvironment (TME), and treatment‑related adverse effects. The present review offers a comprehensive synthesis of the immunotherapeutic paradigm in BC, spanning ICIs, adoptive cellular therapies (CAR-T, CAR-NK, CAR-M, TIL, TCR-T, and CIK cells), and emerging immune modulators. We critically evaluate pivotal clinical trials, discuss cross-cutting challenges—including biomarker development, therapy resistance, and the practical limitations of cellular products—and highlight rational combinatorial strategies. By contrasting the translational readiness of diverse modalities and outlining a framework for personalized therapy, this review aims to inform future research and clinical practice in harnessing immunity against BC.

Factors influencing the efficacy of programmed cell death protein 1 / programmed death-ligand 1 inhibitors in non-small cell lung cancer

Current evidence supports PD-L1 as the most widely implemented biomarker, but no single factor adequately captures the biological and temporal heterogeneity of treatment response, so integrated, dynamic, and context-specific biomarker models are required to improve precision immuno-oncology.

Efficacy and Safety of Immune Checkpoint Inhibitors for Recurrent or Metastatic Cervical Cancer: A Systematic Review and Meta-Analysis

Cervical cancer is a major global health challenge and requires the exploration of novel treatment strategies. Immune checkpoint inhibitors, particularly those targeting Programmed Death 1 (PD-1) and Programmed Death-Ligand 1 (PD-L1), have emerged as promising therapeutic agents in oncology. This study aimed to evaluate the efficacy and safety of these inhibitors in the treatment of cervical cancer. A comprehensive literature search was conducted across PubMed, Embase, Web of Science, Scopus, the Cochrane Library, and the China National Knowledge Infrastructure to identify studies published up to November 1, 2024. A total of 26 relevant studies were included, including 21 Non-Randomized Controlled Trials (Non-RCTs) and 5 Randomized Controlled Trials (RCTs). The analysis primarily evaluated the efficacy and safety of PD-1/PD-L1 inhibitors in patients with advanced cervical cancer. The primary outcomes included the objective response rate, disease control rate, progression-free survival, overall survival, and adverse events. Non-RCTs and RCTs were evaluated using ROBINS-I and ROB 2, respectively. Data analysis and visualization were performed using STATA 17.0 and GraphPad. This study has been registered with PROSPERO (registration number CRD42024510357). Therapeutic outcomes indicated that the objective response rate in patients with cervical cancer was 44.30% (95% CI 31.06%–57.93%), and the disease control rate was 63.05% (95% CI 51.67%–73.78%). The complete response, partial response, stable disease, and progressive disease rates were 12.58% (95% CI 6.46%–20.13%), 26.87% (95% CI 19.92%–34.40%), 17.95% (95% CI 12.50%–24.07%), and 27.61% (95% CI 17.68%–38.71%), respectively. The median PFS was 6.22 months (95% CI 3.86–8.59), with 6- and 12-month PFS rates of 58.93% (95% CI 47.78%–69.65%) and 45.20% (95% CI 32.73%–57.96%), respectively. The median OS was 14.81 months (95% CI 8.45–21.16), with 6- and 12-month OS rates of 86.57% (95% CI 80.92%–91.42%) and 70.34% (95% CI 61.47%–78.53%), respectively. Regarding safety, the incidence of treatment-related adverse events was 83.24% (95% CI 73.93%–90.94%), serious adverse events was 25.71% (95% CI 15.33%–37.58%), adverse drug reactions was 71.57% (95% CI 57.61%–83.78%), and immunerelated adverse events was 34.26% (95% CI 27.11%–41.76%). Common treatment-related adverse events included anemia, diarrhea, nausea, and leukopenia. The findings indicate that immune checkpoint inhibitors represent a potentially effective treatment option for patients with cervical cancer; however, their safety profile warrants careful consideration. Combination therapies involving PD-1 inhibitors appear to improve efficacy while maintaining manageable safety.

Immune checkpoint inhibitor-based combinatory and alternative strategies for immune treatment of lung cancers

Immune checkpoint inhibitors (ICIs), particularly antibodies targeting PD-1/PD-L1 and CTLA-4, have reshaped the treatment landscape of lung cancers, most notably non-small cell lung cancer (NSCLC). Nevertheless, only a subset of patients achieve durable benefit due to primary and acquired resistance that arises from tumor-intrinsic factors (e.g., oncogenic drivers and adaptive signaling), tumor-extrinsic determinants in the tumor microenvironment (TME) (e.g., impaired T-cell infiltration and immunosuppressive myeloid populations), and the dynamic evolution of biomarkers. Accordingly, current clinical and translational efforts in lung cancer focus on rational combination strategies—ICIs with chemotherapy, radiotherapy, and targeted agents (including RTK- and KRAS-pathway inhibitors)—as well as alternative approaches that modulate antigen presentation, myeloid regulation, and cancer stemness. In this review, we define a lung cancer–centered scope and summarize (i) established and emerging ICI-based regimens in lung cancer, (ii) mechanisms of resistance relevant to NSCLC and SCLC, (iii) biomarker integration for patient selection and monitoring, and (iv) future directions to optimize efficacy and safety through combinatory and alternative immunotherapeutic strategies.

Primary and acquired resistance to immunotherapy in NSCLC

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer incidence and mortality worldwide. In recent years, immune checkpoint inhibitors (ICIs), particularly those targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) axis, have significantly improved survival outcomes in a subset of patients. However, the magnitude and durability of clinical benefit vary considerably according to PD-L1 expression, treatment setting, histological subtype, oncogenic driver status, and whether ICIs are administered as monotherapy or in combination regimens. A substantial proportion of patients therefore exhibit either primary resistance or acquired resistance after an initial response. This review systematically summarizes the key mechanisms underlying immune resistance in lung cancer. These include defects in antigen presentation, such as abnormalities in major histocompatibility complex class I (MHC-I), transporter associated with antigen processing 2 (TAP2), and β2-microglobulin (B2M), as well as dysregulation of the interferon-γ/Janus kinase-signal transducer and activator of transcription (IFN-γ/JAK-STAT) signaling pathway. Tumors frequently exhibit an immune-excluded or ‘cold’ phenotype, which further limits immune recognition and reduces responsiveness to immunotherapy. This review summarizes immune resistance in NSCLC through a framework that distinguishes primary resistance from acquired resistance. Primary resistance reflects failure of immune activation at treatment initiation, usually due to pre-existing tumor-intrinsic or microenvironmental barriers, including impaired antigen presentation, defective IFN-γ/JAK-STAT signaling, low tumor immunogenicity, immune-cold or immune-excluded phenotypes, and suppressive TME states. In contrast, acquired resistance reflects adaptive tumor and immune ecosystem evolution under therapeutic pressure, leading to neoantigen loss, HLA or B2M alterations, compensatory checkpoint activation, progressive T cell exhaustion, TME remodeling, and epigenetic stabilization of immune escape. We further discuss mechanism-based biomarkers, translational correlates, and rational therapeutic strategies for overcoming resistance.

Next-Generation Checkpoint Combinations: Optimizing PD-(L)1–Based Therapy Across the Advanced, Adjuvant, and Neoadjuvant Settings