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Review
. 2020 Feb 18:11:223.
doi: 10.3389/fimmu.2020.00223. eCollection 2020.

Sensitizing the Tumor Microenvironment to Immune Checkpoint Therapy

Rachael M Zemek  1 , Wee Loong Chin  2   3   4 , Anna K Nowak  2   3   4 , Michael J Millward  3   4 , Richard A Lake  2   5 , W Joost Lesterhuis  1   2   5
Affiliations
Review

Sensitizing the Tumor Microenvironment to Immune Checkpoint Therapy

Rachael M Zemek et al. Front Immunol. .

Abstract

Immune checkpoint blockade (ICB) has revolutionized cancer treatment, providing remarkable clinical responses in some patients. However, the majority of patients do not respond. It is therefore crucial both to identify predictive biomarkers of response and to increase the response rates to immune checkpoint therapy. In this review we explore the current literature about the predictive characteristics of the tumor microenvironment and discuss therapeutic approaches that aim to change this toward a milieu that is conducive to response. We propose a personalized biomarker-based adaptive approach to immunotherapy, whereby a sensitizing therapy is tailored to the patient's specific tumor microenvironment, followed by on-treatment verification of a change in the targeted biomarker, followed by immune checkpoint therapy. By incorporating detailed knowledge of the immunological tumor microenvironment, we may be able to sensitize currently non-responsive tumors to respond to immune checkpoint therapy.

Keywords: CTLA4; PD-1; biomarkers; cancer immunotherapy; immune checkpoints; sensitization; systems biology; tumor microenvironment.

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Figures

Figure 1
Figure 1
Diagram illustrating factors characteristic of a non-responsive tumor microenvironment. Tumors that are non-responsive to checkpoint blockade display resistance at the physical, cellular, protein, and gene expression level. Figures made in ©BioRender-biorender.com.
Figure 2
Figure 2
Diagram illustrating ways a checkpoint blockade favorable tumor microenvironment may be therapeutically attained. Approaches that could alter the non-responsive tumor microenvironment and sensitize tumors to checkpoint blockade. Figures made in ©BioRender-biorender.com.
Figure 3
Figure 3
A personalized pre-treatment strategy to optimize outcomes to immune checkpoint blockade. We propose a pre-treatment approach to treating cancer patients, where tumors displaying features of a non-responsive TME can be first sensitized to attain a favorable TME, to improve chances of response to immune checkpoint blockade. Figures made in ©BioRender-biorender.com. Adapted from a figure we published recently in Science Translational Medicine (7).
See this image and copyright information in PMC

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