CXCR6 (C-X-C Motif Chemokine Receptor 6)

Comprehensive single-cell analysis identified selective chemokine recruitment signatures supporting γδ T-cell infiltration but revealed paradoxical corecruitment of immunosuppressive populations. Patient stratification through chemokine profiling, combined with γδ T-cell enrichment and targeted chemokine antagonism, represents a rational therapeutic strategy.

Additionally, in a Dextran Sulfate Sodium (DSS)-induced colitis model combined with single-cell RNA sequencing, PUT supplementation resulted in the elimination of CXCR6+ CD8+ T cells in the colon. These findings provide new insights into how polyamine metabolism, particularly involving extracellular PUT, impairs the anti-tumor activity of CXCR6+CD8+ T cells, potentially contribut ing to CRC progression.

On the other hand, depletion of DE Tfh cells via Ezh2 gene deletion, inhibition of EZH2 (using FDA-approved drug, tazemetostat), or anti-CXCR6 mAb led to tumor regression. These findings may be relevant to a subset of human AITL cases since we found that ~20-30% of AITL patient samples have concomitantly elevated expression of CXCR6, IL-18R1, and IFNG. Our study identified a pathogenic Tfh-like subset essential for AITL tumor progression in a mouse model and suggests that identifying and targeting a DE Tfh-like subset in AITL patients might be an effective strategy.

To optimize this strategy, we develop Y101S, an antibody-drug conjugate targeting TGF-β, PD-L1, and STING, which demonstrates superior tumor control and immune modulation in preclinical models. These findings highlight the therapeutic potential of this triple-targeting approach.

These T cells appear to mediate antitumor activity potentially through the CXCR6-PI3K-AKT signaling axis. In summary, the LEN-TAP protocol demonstrates promising efficacy and acceptable tolerability as a conversion therapy in uHCC, with peripheral HLA-DR+CD38+CD8+ T cell abundance serving as a potential predictor of therapeutic benefit.

Targeting the MDK/LRP1 axis with Resmetirom offers a promising therapeutic strategy for MASH-associated HCC, addressing both metabolic dysfunction and tumor progression.

As the ligand of CD103, E-cadherin expression increased in tumor cells after irradiation, potentially mediating E-cadherin-CD103 interactions between tumor cells and tissue-resident memory T cells. Our study introduces a novel dual-targeting CD133/PD-L1 CAR-T cell, and further demonstrates the efficacy and rationale of the triple combination approach in solid tumors.

The major risk factor for ICI myocarditis is the use of combination ICI treatment, especially when relatlimab, a novel anti-LAG-3 (lymphocyte-activation gene 3) antibody, is combined with anti-PD-1 (programmed cell death protein 1) therapy...Treatment with anti-CXCR6 antibody prevented premature lethality, attenuated arrhythmias, and reduced the histological severity of myocarditis, demonstrating that CXCR6+ T cells are necessary for disease pathogenesis. Our findings suggest that ICI myocarditis is driven by an expansion of CXCR6+ T cells and identifies CXCR6 as a putative therapeutic target for this highly morbid condition.

In TLSs, TGF-β orchestrated BHLHE40 expression in TRM and effector TRM differentiation. Our findings identified an effector subset of TRM as CD49a+PD1hi CD8+ TRM, and highlighted a BHLHE40-orchestrated, resident immune component, rather than circulating cells, as a major contributor to allograft rejection.

Crucially, this CR code reveals that immunotherapy actively reshapes T-cell trafficking patterns, uncovering profound heterogeneity within conventional populations and distinguishing potent anti-tumor progenitors from cells predisposed to exhaustion or off-target migration. This work establishes CR co-expression as a practical tool, providing a surface marker-based strategy to identify and enrich optimized T cells for adoptive therapies, thereby offering a framework to uncouple efficacy from toxicity.

Increase in liver CD4+ T cell infiltration characterizes MASH-to-HCC progression. These immune signatures combined with clinical parameters demonstrate remarkable predictive value for identifying high-risk MASH patients.

CXCR6 antagonism with SBI-457 can modulate β-catenin activation and may help overcome sorafenib resistance in selected HCC models. These findings support further development of CXCR6 antagonists as single agents or combination therapies to improve treatment outcomes in HCC.