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CAR-T cell therapy for breast cancer: Current status and future perspective.
Cancer Treat Rev
December 2024
Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Napoli, Italy. Electronic address:
Within the expanding therapeutic landscape for breast cancer (BC), metastatic breast cancer (MBC) remains virtually incurable and tend to develop resistance to conventional treatments ultimately leading to metastatic progression and death. Cellular immunotherapy (CI), particularly chimeric antigen receptor-engineered T (CAR-T) cells, has emerged as a promising approach for addressing this challenge. In the wake of their striking efficacy against hematological cancers, CAR-T cells have also been used where the clinical need is greatest - in patients with aggressive BCs.
View Article and Find Full Text PDFDendritic cells type 1 control the formation, maintenance, and function of tertiary lymphoid structures in cancer.
bioRxiv
December 2024
Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Tertiary lymphoid structures (TLS) are organized immune cell aggregates that arise in chronic inflammatory conditions. In cancer, TLS are associated with better prognosis and enhanced response to immunotherapy, making these structures attractive therapeutic targets. However, the mechanisms regulating TLS formation and maintenance in cancer are incompletely understood.
View Article and Find Full Text PDFAntigen presentation by tumor-associated macrophages drives T cells from a progenitor exhaustion state to terminal exhaustion.
Immunity
December 2024
Department of Neurosurgery, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address:
Whereas terminally exhausted T (Tex_term) cells retain anti-tumor cytotoxic functions, the frequencies of stem-like progenitor-exhausted T (Tex_prog) cells better reflect immunotherapeutic responsivity. Here, we examined the intratumoral cellular interactions that govern the transition to terminal T cell exhaustion. We defined a metric reflecting the intratumoral progenitor exhaustion-to-terminal exhaustion ratio (PETER), which decreased with tumor progression in solid cancers.
View Article and Find Full Text PDFCBL0137 and NKG2A blockade: a novel immuno-oncology combination therapy for Myc-overexpressing triple-negative breast cancers.
Oncogene
December 2024
QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
The MYC proto-oncogene is upregulated in >60% of triple-negative breast cancers (TNBCs), it can directly promote tumor cell proliferation, and its overexpression negatively regulates anti-tumor immune responses. For all these reasons, MYC has long been considered as a compelling therapeutic target. However, pharmacological inhibition of MYC function has proven difficult due to a lack of a drug-binding pocket.
View Article and Find Full Text PDFNutrient-driven histone code determines exhausted CD8 T cell fates.
Science
December 2024
NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA.
Exhausted T cells (TEX) in cancer and chronic viral infections undergo metabolic and epigenetic remodeling, impairing their protective capabilities. However, the impact of nutrient metabolism on epigenetic modifications that control TEX differentiation remains unclear. We showed that TEX cells shifted from acetate to citrate metabolism by downregulating acetyl-CoA synthetase 2 (ACSS2) while maintaining ATP-citrate lyase (ACLY) activity.
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