The biocompatibility and targeting efficiency of bacterial EVs position them as a novel therapeutic platform for gastrointestinal cancers. This study provides the first preclinical evidence supporting the use of non-pathogenic bacterial exosomes in oncology, highlighting their translational potential for improving treatment outcomes in pancreatic cancer.

Our study molecularly identifies a key role of SLAMF7 in cholesterol metabolism and trafficking between HCC cells and macrophages and gives a rationale for targeting IL-7 signaling as an effective strategy to sensitize HCC to immunotherapy.

This combination shows promising effects and good safety in patients with HCC who have received liver transplants. Such a method offers a fresh choice for treating those who are thought not to be suitable for immunotherapy, so it needs to be tested in more extensive controlled research.

Furthermore, this platform yielded nanobodies that can be directly reformatted into other therapeutic modalities, including chimeric antigen receptors and bispecific antibodies, while maintaining cytotoxic function. Overall, the E-A screening platform links antibody discovery directly to T-cell function, providing a robust approach for identifying therapeutic antibodies, especially neoantigen-specific nanobodies, for T cell-based cancer immunotherapy.

In this study, we used sequential mutation and sorting techniques to rapidly evolve a PD-1 molecule that exhibits high affinity for PD-L1 while avoiding the recognition by five of the six clinically approved anti-PD-1 drugs. Experimental results verify that the Fc fusion protein and switch receptor based on such PD-1 mutant enhance the efficacy of therapeutic T cells.

Furthermore, LyoBT served as a drug delivery platform for immune checkpoint inhibitors (aPD-L1), with LyoBT@aPD-L1 demonstrating enhanced therapeutic efficacy. Our findings highlight the potential of LyoBT as a dual-functional strategy to combat both lung metastases and their associated fibrosis, offering a promising new avenue for bacterial-based cancer immunotherapy.

Moreover, combination with PD-1 blockade markedly improved tumor suppression, cytotoxic T-cell infiltration, and survival outcomes. Collectively, this work establishes D15 as a multifunctional immunoactive nanocarrier with considerable potential for the construction of next-generation cancer nanovaccines.

Additionally, LDHA siRNA regulated lactic acid metabolism to reverse the immunosuppressive TME. This work provides a paradigm for lactic acid metabolism and ICD mediated GBM treatment, with potential clinical applicability for improving GBM immunotherapy.

Targeting cPLA2α may overcome PD-1 blockade resistance, particularly benefiting patients with high cPLA2α and low baseline PD-L1. This study highlights cPLA2α as a promising therapeutic target to enhance ICI efficacy and reshape LUAD immunotherapy strategies.

ANTXR1 functions as a stromal-associated immunomodulatory driver of tumor progression and immune suppression, representing a promising biomarker and therapeutic target in stromal-rich cancers.

The diabody also led to a significant increase in T-cell proliferation and cytokine release in the MLR assay. This bispecific diabody can be considered a promising checkpoint inhibitor candidate, although more in vitro and in vivo biological function evaluations still need to be performed.

FN1+ TAMs, enriched in sarcomatoid-differentiated ccRCC, mediate immune suppression and confer resistance to immunotherapy. FN1 blockade remodels the TIME, promotes tumor apoptosis, and represents a potential therapeutic strategy in ccRCC.