TIGIT, as a potential immune checkpoint target for immunotherapy of breast cancer

Med Oncol. 2025 Aug 5;42(9):407. doi: 10.1007/s12032-025-02955-3.

Abstract

Breast cancer ranks among the most critical cancers globally due to its elevated prevalence, with an excess of 2.3 million newly reported cases, and it's devastating toll, resulting in a substantial number of fatalities annually. Its significance stems from its complex origins, which include intersecting genetic mutations like breast cancer type 1 susceptibility protein 1/2 (BRCA1/2) that impair DNA repair and heighten hereditary risk, alongside hormonal factors and lifestyle influences. These elements collectively drive tumor development, making it a multifaceted challenge. The development of treatment approaches has advanced from conventional methods, including chemotherapy, surgical tumor resection, hormone therapy, and radiotherapy, to the incorporation of immunotherapy. Within breast cancer immunotherapy, immune checkpoints have gained prominence for their role in tumor evasion, with emerging T-cell immunoreceptor with Ig and ITIM domains (TIGIT) as a key player. TIGIT, a suppressive identified on T and NK cells, contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) domain and binds CD155 to hinder immune responses, promoting tumorigenesis by inducing the depletion of cytotoxic lymphocytes and fostering an immunosuppressive microenvironment. Various studies indicate that this mechanism weakens immune responses against tumors and suppresses the release of inflammatory cytokines, thereby facilitating carcinogenesis. It has been established that blocking TIGIT may restore the functional capabilities of NK and T cells, leading to tumor reduction and an augmented immune response, as demonstrated by favorable results across multiple experimental models. This review explores TIGIT's expression, prognostic value, and therapeutic potential in breast cancer, highlighting how its inhibition disrupts immune suppression and boosts tumor control.

Keywords: Breast Cancer; Immune checkpoint; Immunotherapy; Prognosis; TIGIT; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / immunology
  • Breast Neoplasms* / therapy
  • Female
  • Humans
  • Immune Checkpoint Inhibitors* / pharmacology
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy* / methods
  • Receptors, Immunologic* / antagonists & inhibitors
  • Receptors, Immunologic* / immunology
  • Receptors, Immunologic* / metabolism
  • Tumor Microenvironment / immunology

Substances

  • TIGIT protein, human
  • Receptors, Immunologic
  • Immune Checkpoint Inhibitors