PD-L1 overexpression

GeoMx enabled highly multiplexed gene expression analysis, whereas RNAscope provided better sensitivity and single-cell resolution. The choice of method should be guided by study objectives.

Large-scale prospective studies are needed for validation. https://www.crd.york.ac.uk/PROSPERO, identifier CRD420251048602.

Overexpression of the transcription factor c-Jun increased intratumoral PD-1+TCF1+ CAR T cells but did not prevent exhaustion, given that PD-1 induced posttranscriptional c-Jun down-regulation. PD-L1 blockade restored c-Jun levels, markedly increased CAR T cells, and enabled near-complete tumor clearance, revealing a mechanism by which MHC-independent CAR T cells can be engineered to overcome resistance to PD-1-PD-L1 blockade.

To counteract this resistance mechanism, we developed a TME-responsive nanogel (pirfenidone@nanogel-hyaluronidase-anti-PD-L1 [PFD@NGHP]) for rescuing radiosensitization...This effect synergized radiotherapy to sustain tumor regression and generate abscopal effects. Collectively, our study demonstrates that PFD@NGHP targets the TGF-β1-PD-L1 axis in a cascading manner, offering a promising clinical strategy to overcome the adaptive radioresistance of irradiated pancreatic ductal adenocarcinoma while providing a potential platform for translational nanomedicine evaluation.

Herein, we present a case of advanced MSS gastric cancer with liver and bulky lymph node metastases, in which combination therapy with S-1 plus oxaliplatin (SOX) and nivolumab led to a pathological complete response...This case illustrates that even in MSS gastric cancer with low TMB levels, exceptionally high PD-L1 expression may predict a profound response to ICI-based therapy. The PD-L1 CPS may serve as a critical biomarker independent of TMB or microsatellite-instability status.

Pembrolizumab is a cost-effective first-line treatment for advanced NSCLC with PD-L1 TPS ≥ 50% in Japan. Nivolumab plus ipilimumab is also a viable option. Atezolizumab is the least cost-effective.

The patient was later hospitalized for "recurrent hemoptysis" and received pemetrexed adjuvant chemotherapy combined with cisplatin...Consequently, a targeted therapy regimen combining low to moderate doses of dabrafenib and trametinib was initiated...Moreover, only one low-grade immune-related adverse event was observed during the course of immunotherapy. Patients with advanced NSCLC and BRAF mutations who cannot tolerate targeted therapy are expected to benefit from immunotherapy.

In conclusion, EZH2 overexpression promotes immune evasion in LUAD by suppressing CCL5-mediated T-cell recruitment and MHC class I antigen presentation. Targeting EZH2 augments antitumor immunity, supporting its therapeutic potential in combination immunotherapy strategies.

Our study developed a novel immune classification system for TNBC, identifying CXCL9 as a key biomarker positively correlated with ICB response and regulated by IDO1. These findings provide a basis for precision immunotherapy in TNBC and support the exploration of IDO1 inhibitors in combination with ICB.

Mechanistic studies reveal that RT + BET inhibition accentuates RT-induced DNA damage and micronuclei formation, increases Major Histocompatibility Complex class I and II expression on macrophages, enhances translocation of calreticulin to the plasma membrane, and blocks RT-induced Programmed Death-Ligand 1 (PD-L1) overexpression on tumor cells, thereby promoting immunogenic cell death. Our data suggest that a combination of RT + BET inhibition promotes robust anti-tumor immunity and immunological memory in immunologically cold tumors, thereby opening potential avenues for clinical translation.

We found that irTD is common, clinically manageable, and strongly associated with improved PFS in PD-L1-high metastatic NSCLC treated with pembrolizumab. Thyroid dysfunction may serve as a feasible on-treatment biomarker of effective immune activation, warranting further prospective validation.

Additionally, emerging biomarkers and ctDNA-based MRD surveillance hold promise for refining precision of perioperative treatment. Taken together, the evidence supports perioperative immunotherapy as a forward-looking, evidence-based approach to improving outcomes in resectable NSCLC.