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PI3K/AKT/mTOR and PD‑1/CTLA‑4/CD28 pathways as key targets of cancer immunotherapy (Review)

Shuangcui Wang1,2,3, Changyu Liu1,4, Chenxin Yang3,5

  • 1Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China.

Oncology Letters
|October 11, 2024
PubMed

Insights

This review explores how T cell metabolism, influenced by programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and CD28 pathways, impacts cancer immunotherapy. Understanding these interactions is crucial for developing effective cancer treatments.

Area of Science:

  • Immunology
  • Oncology
  • Cell Metabolism

Background:

  • T cells are critical in cancer immunity, with their function influenced by metabolic state.
  • Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) show promise in cancer therapy.
  • The role of CD28 and its downstream signaling in T cell metabolism requires further elucidation.

Purpose of the Study:

  • To review the interplay between PD-1, CTLA-4, CD28 pathways, and PI3K/AKT/mTOR signaling in T cell metabolism.
  • To explore the clinical applications of these pathways in cancer immunotherapy.
  • To provide a theoretical foundation for advancing cancer immunotherapy strategies.

Main Methods:

  • Comprehensive literature search across PubMed, Scopus, Web of Science, and Cochrane Library.
  • Keywords included 'lung cancer' and 'immunotherapy' to ensure broad coverage.
  • Systematic review and synthesis of existing research on T cell metabolism and immune checkpoints.

Main Results:

  • T cell metabolism significantly impacts T cell proliferation and differentiation, crucial for anti-cancer responses.
  • PD-1, CTLA-4, and CD28 pathways modulate T cell metabolism, affecting their anti-tumor activity.
  • The PI3K/AKT/mTOR pathway is a key downstream mediator linking CD28 signaling to T cell metabolic reprogramming.

Conclusions:

  • Understanding the intricate relationship between immune checkpoints, CD28, and T cell metabolism is vital for optimizing cancer immunotherapy.
  • Targeting these pathways offers potential for enhancing anti-tumor immunity and improving clinical outcomes in cancer patients.
  • Further research into the metabolic regulation of T cells by PD-1, CTLA-4, and CD28 is warranted to develop novel therapeutic strategies.
Keywords:
PI3K/AKT/mTORT cellscancermetabolismprogrammed cell death protein 1/cytotoxic T-lymphocyte associated protein 4/CD28proliferation

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