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Adenosine Phosphate Signaling Boosts Antitumor Immunity and Amplifies Melanoma Immunotherapy Success
- Research from Central South University highlights the impact of adenosine phosphate signaling on the melanoma tumor microenvironment (TME) and antitumor immunity.
- Purinergic signaling through P2 receptors, responsive to adenosine nucleotides like ATP and ADP, plays a crucial role in orchestrating immune responses and metabolic reprogramming in the TME.
- Melanoma tumors were categorized into different adenosine phosphate signaling subtypes, revealing distinct metabolic and inflammatory features.
- High APsig tumors, characterized by elevated P2 receptors, showed increased immune activation, antigen processing, and better immune cell infiltration.
- The Adenosine Phosphate Signaling Model (APsig) correlated elevated APsig levels with improved overall survival, particularly in patients treated with immune checkpoint inhibitors.
- Single-cell RNA sequencing revealed that myeloid cells exhibit pronounced activation of APsig, contributing to enhanced antigen presentation and immune responses.
- High APsig tumors displayed reduced immunosuppressive elements and increased cytotoxic T cell infiltration, indicative of a favorable antitumor immune response.
- APsig emerges as a potent biomarker for predicting responses to immune checkpoint therapies, surpassing traditional markers like TMB and PD-L1 expression.
- Pharmacological modulation of adenosine phosphate signaling pathways could enhance the efficacy of immunotherapies by overcoming immune evasion mechanisms and metabolic constraints.
- The study suggests the potential of APsig in guiding personalized combination therapies across various solid tumor types, revolutionizing cancer treatment approaches.
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