CXCR4 (Chemokine (C-X-C motif) receptor 4)

Transcriptomic profiling further revealed upregulation of CXCR4 and BCL6 following Forskolin treatment, and functional blockade of these pathways attenuated the beneficial effects of Forskolin, underscoring their critical roles in reinforcing CAR-T cell stemness. Our findings highlight a novel strategy that integrates stem cell-reprogramming agents to enhance CAR-T cell stemness and provide potential therapeutic targets to improve the efficacy of CAR-T cell therapy against solid tumors.

Cytokine-driven signaling within the TME plays a central role in therapy resistance. Protein profiling studies have contributed mechanistic insight into these interactions and helped define resistance-associated pathways across treatment settings. Ongoing clinical studies will determine how targeting these pathways can be most effectively applied to improve patient outcomes.

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.

In our exploratory analysis, [¹⁸F]FDG-uptake within medullary concordant lesions was linked to both response and survival, while CXCR4-expressing medullary volume and sDmax added survival information. Concordance-aware, lesion-level quantification from dual-tracer PET/CT might present as a promising approach to aid risk stratification for CXCR4-directed RPT. However, initial findings of our hypothesis generating analysis warrant prospective validation in larger cohorts.

Our findings demonstrate that immune resistance in FLC is mediated by both local T-cell exclusion and exhaustion, with combination CXCR4 and PD-1 blockade acting cooperatively to overcome these independent mechanisms. These results highlight the versatility of the human TSC system to aid in the study of rare cancer types and provide important preclinical evidence for the rational design of combination immunotherapy in FLC, which currently lacks any effective systemic therapy.

Logistic regression analysis indicated that CXCL12 and CXCR4 play a crucial role in postoperative lymph node metastasis, and the elevated expression of these proteins is more associated with lymph node metastasis. The elevated CXCL12 and CXCR4 in tumor tissues are strongly linked to postoperative lymph node metastasis, suggesting that these proteins may be crucial in the NSCLC lymph node metastasis and highlighting their potential as predictors of metastasis risk.

Differential gene expression confirmed elevated levels of MIF, CD74, CD44, and SPP1 in tumor tissues, while pathway enrichment analyses highlighted cytokine signaling, antigen presentation, and chemokine-regulated immune modulation as key biological processes. Collectively, our study provides a high-resolution map of CRC intercellular communication and identifies MIF-CD74-associated signaling as a central immunoregulatory hub with potential relevance for therapeutic targeting and biomarker development.

Fraction-specific analyses showed stronger induction of IL-23R and IL-23R complex expression in PF compared with RF. These findings identify an intraclonal bias toward IL-23 responsiveness in the CLL cells with a phenotype of recently divided, tissue-emigrated cells and suggest the IL-23/IL-23R axis as a potential therapeutic target.

P2, N=80, Not yet recruiting, Australasian Leukaemia and Lymphoma Group

In this study, we successfully constructed NGR peptide-modified Exos derived from CAFs for the targeted delivery of Res. This work innovatively proposes a novel immunotherapeutic strategy that targets tumor-associated MDSCs rather than directly killing tumor cells. Mechanistically, we identify and validate CXCR2 as a previously unrecognized functional target of resveratrol in MDSCs, through which resveratrol suppresses NF-κB signaling and reprograms MDSC function. Collectively, NGR-Exos@Res represents a precise and efficient delivery platform capable of reversing the immunosuppressive microenvironment in LC and provides a promising combinatorial strategy to overcome immunotherapy resistance by targeting immunosuppressive myeloid cells.

Immunohistochemistry further confirmed the prognostic value of key regulatory proteins (RGS1, CXCR4, CTLA4, ARPP19, ZNRF1, and ZNF207). Our findings highlight the metabolic immune crosstalk in GC and provide a promising biomarker panel for precision risk stratification and potential immunotherapeutic targets.