Heat up and Destroy: Immunotherapy of “Cold” Tumors Using the Example of Glioblastoma

TL;DR

This paper reviews strategies to make 'cold' tumors like glioblastoma respond better to immunotherapy by altering their immune environment.

Contribution

The paper highlights oncolytic virus-based combinations as a promising approach for treating 'cold' tumors.

Findings

Glioblastoma's tumor microenvironment is 'cold', limiting immunotherapy effectiveness.

Oncolytic viruses show potential in preclinical and clinical studies for treating 'cold' tumors.

Combination therapies may alter the immune landscape of 'cold' tumors.

Abstract

The characterization of tumors as either “hot” or “cold” is determined by intrinsic properties of the cancer cells, the characteristics of the tumor immune landscape, the composition of the tumor microenvironment (TME), and underlying signaling mechanisms. These biological factors are critical in defining the clinical outcomes and therapeutic responses observed in cancer patients. The TME of glioblastoma exemplifies a case of “cold” TME, which significantly hinders antitumor immunity. This constitutes the predominant rationale underlying the ineffectiveness of immunotherapy. This review provides a thorough analysis of contemporary immunotherapeutic strategies that have been developed for the purpose of altering the immunological characteristics of tumors, with a view to achieving their effective elimination. The core mechanisms of action and future clinical applications of immune checkpoint inhibitors, adoptive cellular therapy, and oncolytic viruses (OV) are delineated. A combination of preclinical and clinical evidence suggests that OV-based combinations could be an effective treatment strategy for “cold” tumors.

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