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Review
. 2022 Sep 5:12:955163.
doi: 10.3389/fonc.2022.955163. eCollection 2022.

Overcoming resistance to PD-1/PD-L1 inhibitors in esophageal cancer

Chao Cheng  1 , Lingdun Zhuge  2 , Xin Xiao  1 , Siyuan Luan  1 , Yong Yuan  1
Affiliations
Review

Overcoming resistance to PD-1/PD-L1 inhibitors in esophageal cancer

Chao Cheng et al. Front Oncol. .

Abstract

As the predominant treatment option of the immunotherapy for advanced esophageal cancer (EC), the application of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors brings new hope to clinical practice. However, a considerable portion of patients do not response to this therapy, meanwhile most patients sensitive to PD-1 or PD-L1 antibody initially will develop resistance to the treatment eventually. To break through the limits of clinical effect, it is of critical importance to make a profound understanding of the mechanisms of so called primary resistance and acquired resistance. Subsequently, exploring potent predictors to identify suitable patients for anti-PD-1/PD-L1 treatment and investigating efficient strategies to overcome drug resistance will be helpful to expend the benefit of immunotherapy. In the present view, we summarized the potential predictive factors for anti-PD-1/PD-L1 immunotherapy in EC, and demonstrated the plausible mechanisms of resistance to PD-1/PD-L1 blockade as well as its feasible solutions.

Keywords: esophageal cancer; immune checkpoint inhibitors; immunotherapy; programmed death 1; programmed death-ligand 1; resistance.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Key mechanisms of drug resistance to PD-1/PD-L1 inhibitors in EC. MHC: major histocompatibility complex; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; IFN-γ, interferon gamma; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; Treg, regulatory T cell; IDO, indoleamine 2,3-dioxygenase; TAM, tumor associated macrophage; M2, macrophages with M2 phenotype; ICI, immune checkpoint inhibitor; miRNA, microRNA; TMB, tumor mutation burden; MSI, microsatellite instability; TGF-β, transforming growth factor-β; IL-10, interleukin-10.
Figure 2
Figure 2
Overview on the strategies to overcome drug resistance to PD-1/PD-L1 inhibitors in EC. Strategies including suitable predictors and combined therapy, have been proposed to improve the effect of PD-1/PD-L1 inhibitors in EC.
See this image and copyright information in PMC

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