CXCR3 is a chemokine receptor with three ligands: CXCL9, CXCL10 and CXCL11. We report that in addition to attracting CXCR3+ T cells to tumor sites a key role of CXCL9 and CXCL10 is in inducing a self-feeding feedback loop that accelerates effector/cytotoxic activities of both CD4+ and CD8+ T cells while downregulating immunoregulatory protein TIM3. CXCR3KO mice displayed a markedly reduced response to anti-PD-1 and anti-CTLA-4 therapy. Results from a panel of and ex vivo 3D tumor models imply that, beyond driving CD8+ T cells into T-cell exhaustion, a major role of PD-1 and CTLA-4 is in limiting the CXCR3-based self-feeding mechanism of T cell potentiation. This may explain why patients that are CXCL9/CXCL10 tend to respond well to anti-PD-1 therapy, as opposed to patients that are CXCL9/CXCL10. It also suggests a therapeutic role for CXCL9-Fc or CXCL10-Fc therapy; herein we demonstrate significant anti-tumor activity in multiple murine tumor models with such agents.
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http://dx.doi.org/10.3389/fimmu.2024.1452212 | DOI Listing |
Eur J Cancer
November 2024
University of Perugia, Unit of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy.
A unique collaboration of multi-disciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to two-centimeter safety margins. For a correct stage classification and treatment decision, a sentinel lymph node biopsy shall be offered in patients with tumor thickness ≥ 1.
View Article and Find Full Text PDFDiscov Oncol
December 2024
Division of Medical Oncology, Department of Internal Medicine, Ege University Medical Faculty, Izmir, 35100, Turkey.
Immune checkpoint inhibitors (ICIs) have significantly improved the five-year survival rate for advanced melanoma. However, many patients exhibit resistance to ICI therapy. This study evaluated the efficacy and prognostic factors of anti-PD-1 (Group A) and nivolumab-ipilimumab (Group B) therapy in patients with advanced melanoma who were resistant to prior ICI therapy.
View Article and Find Full Text PDFNat Immunol
December 2024
Faculty of Medicine, Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology and Infectious Disease, University Medical Center Freiburg, Freiburg, Germany.
The mechanisms underlying the efficacy of anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) therapy are incompletely understood. Here, by immune profiling responding PD-1CD8 T (T) cell populations from patients with advanced melanoma, we identified differential programming of T cells in response to combination therapy, from an exhausted toward a more cytotoxic effector program. This effect does not occur with anti-PD-1 monotherapy.
View Article and Find Full Text PDFTransl Cancer Res
November 2024
Department of Dermatology, Binhaiwan Central Hospital of Dongguan, Dongguan, China.
Background And Objective: Basal cell carcinoma (BCC) is the most common malignancy of humankind, characterized by its low propensity for metastasis and its high recurrence rate. Surgical intervention is the predominant therapeutic approach. However, for cases of locally advanced BCC (laBCC) and metastatic BCC (mBCC), systematic therapy may be the first option.
View Article and Find Full Text PDFImmunol Res
December 2024
Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
Natural killer (NK) cells are a cytotoxic subset of innate lymphoid cells and have key roles in antitumoral immunity. This study evaluates the roles of immune checkpoint receptors on NK cell phenotype and functions both before and after circulation through tumor tissue. Twenty non-small cell lung cancer patients undergoing surgery and 21 healthy controls were included.
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