CCL19 (C-C Motif Chemokine Ligand 19)

We further detail past and ongoing therapeutic efforts and trials addressing these axes in both PDAC and relevant non-PDAC settings via several small-molecule antagonists and monoclonal antibodies: BMS-813160, Maraviroc, Leronlimab, FLX475, PF-07054894, IDOR- 1117-2520, and CAP-100. Despite continuous advances in the field, the current body of evidence remains limited and presents significant research gaps in areas such as spatial profiling, stage-specific analyses, and general mechanistic validation in PDAC-specific settings. Addressing these shortcomings will be key to developing a more comprehensive knowledge of the field and improving future therapeutic strategies to overcome PDAC.

Notably, 7 × 19 CAR-T cells derived from allogeneic donors also induced epitope spreading in tumor-bearing hosts, thereby increasing survival. The 7 × 19 CAR system is a promising strategy for overcoming antigen heterogeneity in solid tumors by promoting epitope spreading.

Moreover, low-risk patients exhibit better sensitivity to chemotherapy. This novel EMT signature offers excellent potential for predicting the prognosis, tumor immune heterogeneity, and therapeutic responses in breast cancer.

Therapeutically, agents targeting chemokine pathways, most notably the CCR4 monoclonal antibody Mogamulizumab, have demonstrated clinical efficacy, while emerging inhibitors of CCR6, CCR5, and CXCR4 offer promising avenues for intervention. We further highlight how recent single-cell and other high-dimensional omics studies refine cell-type-specific chemokine sources and receptor expression, enabling more precise mapping of chemokine-driven intercellular communication programs in CTCL TME remodeling and better prioritization of therapeutic targets and biomarkers.

In conclusion, these findings show that CCL19 generated by STING/type I IFN/STAT1 pathway in dMMR/MSI-H CRC cells can promote the expansion of memory B cells, which suppresses tumor growth and enhances the efficacy of PD-1 blockade.

H3-7/15 × 19-CAR-T cells significantly improved the therapeutic efficacy of traditional CAR-T cells, including CD19- and H3-CAR-T cells, acting in pancreatic cancer- and non-small cell lung cancer-derived xenograft tumor models based on NOD-Prkdcem26Cd52Il2rgem26Cd22/Nju (NCG) mice. In summary, H3-7/15 × 19-CAR-T cells possess potential for clinical transformation and represent a new strategy for treating solid tumors.

Functional assays demonstrated that GHR overexpression suppressed proliferation, migration, and invasion while promoting apoptosis. Our study integrates bulk and single-cell transcriptomics with functional validation, unveiling cytokine-driven mechanisms in HBV-HCC. The cytokine-based prognostic model holds promise for risk stratification, immunomodulation, and personalized therapy, offering new avenues for improving HBV-HCC management.

By enhancing immune cell infiltration, it remodeled the TME, thereby inducing systemic anti-tumor immunity and even immune memory, without causing severe pathological damage. This study confirmed rPR8-CCL19 as a promising CRC immunotherapy for further exploration.

Functional enrichment and immune infiltration analyses revealed that NETs-high tumors were associated with suppressive immune phenotypes, metabolic reprogramming, and impaired lymphoid chemokine expression (e.g., CCL19, CXCL13). Our findings suggest that NETs not only predict poor prognosis in LUAD but may also impair TLS maturation and local antitumor immunity, highlighting their potential as therapeutic targets.

Remarkably, differentiation stages of key cell type with heterogeneity and the biomarker expression patterns across these stages might be associated with SSc progression. CCL19 and LOXL2 were identified as novel biomarkers for SSc, providing insights into the exploration of the disease's pathogenesis and the development of new therapeutic targets.

CCR7+ DCs expressed both co-stimulatory and co-inhibitory molecules, which may underlie their capacity for antitumor activation and concurrent vulnerability to suppression. Modulating the mechanisms that form and restrain CCR7+ DC perivascular immune hubs may improve cancer immunotherapy.