CXCR5 expression

Mechanistically, C5/IL7-CAR-T cells displayed enhanced STAT5 signaling. These findings highlight the potential of CXCR5 and IL-7 co-expression to improve CAR-T cell therapy efficacy against osteosarcoma.

The C-terminal derivatization of the human chemokines CXCL13 and CXCL10 with bioorthogonal tetrazine-BODIPY and BCN groups retained binding and internalization via their cognate CXCR5 and CXCR3 receptors and enabled rapid fluorescence labeling of CXCR5+ CXCR3+ resistant B cells─but not drug-susceptible leukemic cells─via intracellular chemokine ligation. This modular chemical approach offers a versatile strategy for real-time immunophenotyping of cell populations with distinct chemokine profiles and will accelerate the design of new precision medicine tools to advance personalized therapies in blood tumors.

The KEYNOTE-B84 study (NCT04815720) evaluated the safety and efficacy of pepinemab in combination with pembrolizumab as a first-line treatment for immunotherapy-naïve patients with R/M HNSCC. Biomarker studies conducted in patients with surgically resectable metastatic melanoma (NCT03769155) and HNSCC (NCT03690986) received neoadjuvant treatment with pepinemab/nivolumab/ipilimumab combinations compared to nivolumab or ipilimumab alone...Increased density and maturity of lymphoid aggregates correlated with disease control and longer progression-free survival (PFS). Conclusions Pepinemab, a Semaphorin 4D (SEMA4D) blocking antibody, in combination with ICB converts 'Cold' tumors to 'Hot' by inducing organized lymphoid aggregates.

The results obtained in this study suggest that CXCR5 CD19 CAR-T cells should be investigated in a trial with broader patient populations.

P=N/A, N=20, Not yet recruiting, The Affiliated Hospital of Xuzhou Medical University; The Affiliated Hospital of Xuzhou Medical University

Screening and on-treatment tumor biopsies were collected from several clinical trials: the KEYNOTE-B84 study (NCT04815720), that evaluated the safety and efficacy of pepinemab in combination with pembrolizumab as a first-line treatment for immunotherapy-naïve patients with R/M HNSCC, and biomarker neoadjuvant studies conducted in metastatic melanoma (NCT03769155) and HNSCC (NCT03690986) patients with surgically resectable disease treated with pepinemab/nivolumab/ipilimumab combinations compared to nivolumab or ipilimumab alone. When SEMA4D is blocked from binding to its receptors, suppression is reduced, leading to increased penetration and organization of antigen presenting cells (APC) and lymphoid cells in the tumor microenvironment. It is expected that this would facilitate interaction and communication among these cell populations, accounting for improved immune responses in otherwise "cold" tumors.

Our data collectively indicated that however approximately one third of CD4+ lymphocytes expressed CXCR5 and accordingly had the capacity to enter the follicles, less than 2% of them represented Tfh and TFR phenotypes. The percentage of these cells increased in progressed tumors and showed an association with negative prognostic factors.

The transcriptional repressor B cell lymphoma-6 was partially required for their maintenance. Altogether, we propose that the LAG3+CXCR5+ CD4 T cell subset could play a role in maintaining CD4 T cell responses during persistent infections.

Collectively, immature B cells and B2-FO cells are key actors in the control of melanoma growth, but their mobility and functions are differently impaired by IL4I1 overexpression during melanoma progression. Thus, our present data strongly urge us to associate an IL4I1 antagonist with current immunotherapy to improve the treatment of metastatic melanoma.

We found that CXCR5 is widely expressed in neoplastic TFH cells, except in TFHL-NOS, and represents a specific marker of this lymphoma entity. Our results suggest that CXCR5 directs the distribution of neoplastic T cells in the affected lymph nodes and may influence the formation of the pathognomic pathological FDC network.

The regional lymph nodes of breast cancer patients harbor Tfh-like exhausted cytotoxic T lymphocytes with high PD-1 and TIM-3 checkpoint molecule expression. The immunological conditions in the regional lymph nodes should be implicated for immune checkpoint immunotherapy (ICI) of cancer.

NK cell-mediated killing of HIV-1 infected cells by NaMiX represents a promising approach to support HIV-1 cure strategies.

Loncastuximab teserine had a deleterious effect on several hematologic parameters, which was not observed with VIP924 or polatuzumab vedotin. The efficacy and tolerability observed in this study with VIP924 suggests further testing in human clinical trials is warranted.

Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.

Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib, etc.) in addition to inhibition B-cell receptor signaling also significantly influence interactions with the microenvironment. Changes of surface molecules CXCR3, CXCR4, CXCR5, CCR7, CD38 and CD49d expression during ibrutinib treatment and consequent impact on interactions with microenvironment may play an important role in the disease pathogenesis, drug resistance and may reveal new treatment strategies. Current study is ongoing evaluating other molecules involved in interactions within microenvironment and with development of model for tumor distribution and redistribution.