NKG2D (killer cell lectin like receptor K1)

NKG2D-directed CAR-Ms eliminate HCC through integrated innate phagocytosis, adaptive immune activation, and myeloid reprogramming, overcoming key therapeutic barriers. Combination with anti-PD-L1 enhances therapeutic efficacy by leveraging innate-adaptive crosstalk, providing a promising approach for HCC immunotherapy.

Allo-HCT can be a platform for treating NBL using combination ex vivo stimulated allogeneic NK cell therapy with TIM-3 blockade to enhance the GVT effect without inducing GVHD.

This standardized, GMP-compliant protocol provides a robust platform for producing PB-derived CAR-NK cell therapies in a closed platform, advancing their clinical translation.

Mechanisms by which KIR3DL1/Bw4 interaction interferes with BCG-induced NK cell proliferation and the production of cytokines and icNO, warrant further investigation. HLA-I genotyping should be investigated as a useful biomarker to personalize BCG immunotherapy in BC.

As a homeostatic factor, PRDM1 is induced upon IL-2 and feeder cell stimulation, but its ability to restrict NK-cell growth upon feeder stimulation may be counteracted by the AP-1-induced transcriptional network. The loss of PRDM1 activity is frequent in NK-cell malignancies which may lead to decreased homeostatic control, impaired terminal differentiation, enhanced cellular fitness, and the acquisition of more stem-like features, thereby promoting lymphomagenesis.

Furthermore, EHMT2 and TGF-β1 inhibitors suppressed tumors in immunocompetent, but not in immunodeficient mice. These findings establish EHMT2 as a suppressor of NK cell-mediated anti-tumor immunity and a promising therapeutic target.

A significantly diminished percentage of CD8+CD45RA+CD197⁻ T cells, alongside markedly elevated interleukin-6 (IL-6) levels, was observed in non-survivors, strongly supporting their role as key prognostic biomarkers for predicting sepsis-related mortality. Interestingly, tumor necrosis factor-alpha (TNF-α) levels did not significantly differ between those who survived and those who did not, a result that diverges from some prior reports and highlights the possibility of population-specific immunological nuances.

The NK cell/PDO co-culture platform allows the identification of both common and patient-specific impacts of the tumor microenvironment on NK cell function and can aid the development of patient-tailored immunotherapies. The majority of CRC (CMS2/CMS3) PDOs from our cohort were susceptible to NK cell-mediated killing and induced NK cell activation, highlighting the potential of NK cells for CRC immunotherapies.

EPE exerts anti- HCC effects by activating NK cells through the activation of the cGAS-STING signaling pathway. This suggests that EPE may serve as a potential immunotherapeutic agent, offering novel therapeutic perspectives for the treatment of HCC.

IL-35 is upregulated in EGFR-mutant NSCLC and mediates immune suppression by impairing NK cell activity. Targeting IL-35 may offer a therapeutic avenue to restore NK cell function and enhance anti-tumor immunity.

This process augments the antitumor immunity of NK cells while concurrently enhancing their antibacterial function, leading to intensified clearance of Fn and further alleviation of immunosuppression, thereby creating a positive feedback loop. The LYC@Bac biohybrid offers a precise strategy to modulate intratumoral microbiome-immune cell interactions, providing a promising approach for enhanced cancer immunotherapy.

This study demonstrates a peptide-based platform to remodel cold tumor immune microenvironments. Integration of transcriptomic profiling provides mechanistic insights and establishes a robust workflow for evaluating immunomodulatory technologies. This tumor-agnostic approach may enhance anti-tumor immunity and improve immunotherapy efficacy in cold tumors.