CCL22 (C-C Motif Chemokine Ligand 22)

L-Vac demonstrates high in vivo biosafety, breaking down into manganese ions that are primarily excreted through feces. Therefore, chiral adjuvants will pave a brilliant avenue to facilitate cancer immunotherapy.

Tivumecirnon (FLX475) and Zelnecirnon (RPT193), two clinical-stage investigational drugs, bind to the orthosteric site of CCR4, blocking the chemokine recognition site 1. In contrast, AZD2098 and GSK2239633A occupy an allosteric site near the TM7-H8 turn, presumably interfering with G-protein coupling. Further analyses reveal that the therapeutic antibody mogamulizumab binds to the N-terminal region of CCR4 without competing with CCL17, suggesting that its antagonistic effect is mediated exclusively through antibody-dependent cellular cytotoxicity. Together, these structural insights elucidate distinct modes of CCR4 inhibition and provide a framework for the rational design of next-generation therapeutics targeting chemokine receptors.

P=N/A, N=52, Recruiting, Fondazione del Piemonte per l'Oncologia

P=N/A, N=110, Recruiting, Fondazione del Piemonte per l'Oncologia

Focusing on these axes provides mechanistic insights, highlights potential therapeutic targets, and identifies predictive biomarkers. Strategies targeting the chemokine-chemokine receptor axes, including selective receptor blockade, combination with immune checkpoint inhibitors, and omics-based approaches to resolve Treg heterogeneity, offer avenues to reprogram the immunosuppressive TME and enhance antitumor immunity.

In this research, we discovered a novel prognostic signature comprising four genes and classified EC into two distinct molecular subtypes driven by neutrophil-associated genes. These results enhance our understanding of EC's prognostic profile and its immune microenvironment, which may facilitate improved risk stratification and guide the design of personalized treatment approaches.

EGFR-TKI-resistant cell lines were established by long-term exposure to gefitinib, afatinib, and osimertinib via the PC9 model. Targeting endoplasmic reticulum (ER) stress pathways alongside immune checkpoint inhibitors may be crucial for overcoming resistance mechanisms identified here. These insights provide a rationale for personalized treatment strategies tailored to the immune-related gene-expression profiles observed in EGFR-TKI-resistant NSCLC models, aiming to enhance therapeutic responses and improve clinical outcomes.

In contrast, M1-like macrophages could produce CXCL9 and CXCL10, activating effector CD8+ T cells, thereby enhancing anti-tumor immunity. Finally, the promising therapeutic potential of targeting specific chemokine signaling axes, such as CCL2/CCR2 and CXCL10/CXCR3, was discussed as a strategy to improve the efficacy of cancer immunotherapy.

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.

Vitamin D down-regulated the pro-inflammatory and up-regulated the anti-inflammatory cytokines. This indicates that vitamin D can modulate the expression of inflammatory mediators, particularly in a cancer setting. The results support the potential use of vitamin D as an anti-cancer agent with anti-inflammatory properties.

This review provides an updated overview of the immune landscape of tongue SCC, with special emphasis on the CCL22-CCR4 axis and its interaction with histamine signaling. A deeper understanding of CCL22- and histamine-mediated pathways may contribute to the development of more effective and personalized immunotherapy strategies for tongue SCC.

Our results lend support to the presumption that inflammatory cytokines are important biomarkers that associate with DR severity and may represent novel targets for inhibition. The authors have no proprietary or commercial interest in any materials discussed in this article.