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Next-Generation Immune Checkpoints and Tumor Microenvironment Modulation in Cancer Immunotherapy - PubMed

a day ago
  • #immune checkpoints
  • #tumor microenvironment
  • #cancer immunotherapy
  • Immunotherapy has transformed cancer treatment by leveraging the immune system to target and destroy malignant cells.
  • Current immune checkpoint inhibitors (ICIs) like CTLA-4, PD-1, and PD-L1 show durable responses but are limited to a subset of patients due to immune evasion and tumor microenvironment (TME) immunosuppression.
  • Next-generation immune checkpoints include co-inhibitory (LAG-3, TIM-3, TIGIT, VISTA, IGSF8) and co-stimulatory (ICOS, OX40, GITR, 4-1BB, CD40, CD27) pathways, offering new avenues for treatment.
  • Strategies to remodel the TME include targeting immunometabolic pathways (IDO1, CD73), innate immune sensing (TLRs), cytokine signaling (IL-2), micronutrient immunoregulators (vitamin D), and gut microbiota.
  • Predictive features like T cell infiltration, tumor mutational burden (TMB), and microbiome composition can guide combination therapies for broader immunotherapy efficacy.
  • Precision immuno-oncology frameworks using multiomic profiling, AI, and systems biology aim to optimize treatment selection and reduce immune-related toxicities.
  • Emerging technologies like nanomedicine, synthetic biology, and chronotherapy promise to enhance therapeutic specificity and durability in cancer immunotherapy.