Turning cold tumors hot: from molecular mechanisms to clinical applications

Trends Immunol. 2022 Jul;43(7):523-545. doi: 10.1016/j.it.2022.04.010. Epub 2022 May 25.

Abstract

Immune checkpoint blockade (ICB) therapies have achieved clinical benefit, but most 'immune-cold' solid tumors are not responsive. The diversity of immune evasion mechanisms remains a key obstacle in turning nonresponsive 'cold' tumors into responsive 'hot' ones. Therefore, exploring the mechanisms of such transitions and tumor immunotyping can provide significant insights into designing effective therapeutic strategies against cancer. Here, we focus on the latest advances regarding local and systemic regulatory mechanisms of immune responses in cold and hot tumors. We also highlight the necessity for tumor immunotyping through the assessment of multiple immunological variables using various diagnostic techniques and biomarkers. Finally, we discuss the challenges and potential clinical applications of immunophenotyping to turn cold tumors hot, which may further guide combined immunotherapies.

Keywords: combined therapy; immune checkpoint blockade; immunotyping; tumor ecosystem; tumor microenvironment.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Immunity
  • Immunotherapy / methods
  • Neoplasms* / drug therapy
  • Tumor Microenvironment*