TAM-tastic: from resistance to resilience in cancer

Trends Pharmacol Sci. 2024 Nov;45(11):953-954. doi: 10.1016/j.tips.2024.09.006. Epub 2024 Oct 1.

Abstract

Overcoming resistance to immunotherapy in cancer is challenging due, in part, to tumor-associated macrophages (TAMs) co-expressing T cell immunoglobulin and mucin domain-containing 3 (TIM3) and V-domain immunoglobulin suppressor of T cell activation (VISTA) in tumor microenvironments (TME) with sparse T cell infiltration. In a recent article, Vanmeerbeek et al. found that blocking TIM3 or VISTA on IL-4-supported TAMs, in combination with paclitaxel (PTX), reprogrammed TAMs to attack cancer cells, highlighting a potential new therapeutic strategy.

Keywords: cancer immunotherapy; immunogenic cell death; immunoresistant; tumor-associated macrophages.

MeSH terms

  • Animals
  • B7 Antigens / antagonists & inhibitors
  • B7 Antigens / metabolism
  • Drug Resistance, Neoplasm / drug effects
  • Hepatitis A Virus Cellular Receptor 2* / antagonists & inhibitors
  • Hepatitis A Virus Cellular Receptor 2* / metabolism
  • Humans
  • Immunotherapy / methods
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Tumor Microenvironment* / drug effects
  • Tumor Microenvironment* / immunology
  • Tumor-Associated Macrophages / drug effects
  • Tumor-Associated Macrophages / immunology
  • Tumor-Associated Macrophages / metabolism

Substances

  • B7 Antigens
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Paclitaxel
  • VSIR protein, human