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Review
. 2023 Jun 30;14(3):1560-1575.
doi: 10.21037/jgo-22-1133. Epub 2023 May 11.

PD-L1 testing in advanced gastric cancer-what physicians who treat this disease must know-a literature review

Renata D'Alpino Peixoto  1 , Maria Cecilia Mathias-Machado  1 , Alexandre Jácome  2 , Mariana Gil  3 , João Fogacci  3 , Bárbara Sodré  3 , Thaís Passarini  2 , Aline Chaves  2 , Paulo Henrique Diniz  2 , Flora Lino  3 , Alexandre Palladino  3 , Mirela Souto  4 , Ana Carolina de Castro  2 , Bernardo Garicochea  1
Affiliations
Review

PD-L1 testing in advanced gastric cancer-what physicians who treat this disease must know-a literature review

Renata D'Alpino Peixoto et al. J Gastrointest Oncol. .

Abstract

Background and objective: Immune checkpoint inhibition has shed light on a new era in cancer therapy, and randomized clinical trials have demonstrated that a meaningful portion of the overall population of metastatic gastric cancer (GC) patients may derive clinical benefit from immunotherapy, which raises the relevance in identifying predictive biomarkers. Programmed cell death-ligand 1 (PD-L1) expression has demonstrated a significant association between level of expression and the magnitude of benefit derived from immune checkpoint inhibition in GC. Nevertheless, this biomarker shows several pitfalls that must be considered in the therapeutic decision to incorporate immune checkpoint inhibition as the standard of care of GC, such as spatial and temporal heterogeneity, interobserver variability, immunohistochemistry (IHC) assay, and influence by chemotherapy or radiation therapy.

Methods: In the present comprehensive review, we revised the main studies regarding PD-L1 evaluation in GC.

Key content and findings: Here we describe the molecular characteristics of the tumor microenvironment in GC, the obstacles in the interpretation of PD-L1 expression and present the data of the clinical trials that have evaluated the efficacy and safety of immune checkpoint inhibition and the association with the biomarker expression, both in first-line and later lines of therapy.

Conclusions: From the emerging predictive biomarkers for immune checkpoint inhibition, PD-L1 has demonstrated a meaningful association between level of expression in tumor microenvironment and the magnitude of benefit derived from immune checkpoint inhibition in GC.

Keywords: Immunotherapy; gastric cancer (GC); literature review; programmed cell death-ligand 1 (PD-L1).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-1133/coif). RDP reports honoraria for lectures from Servier, BMS, MSD and Lilly. She also reports consulting fees from BMS and Lilly as well as support for attending meetings from Astrazeneca and Daiichi and Advisory Boards from AztraZeneca, Daiichi, BMS, Lilly and Servier. MCMM reports honoraria for lectures from Lilly and support for attending meetins from Pfizer. AJ reports consulting fees from Bayer, Lilly, Servier, BMS and Merck. He also reports honoraria for lectures from BMS and Astellas. MG reports honoraria for lectures from Servier, BMS, MSD, Amgen and Lilly. She also reports support for attending meetings from Pfizer, AstraZeneca and Daiichi. The author receives consulting fees from Servier and BMS and also has participated on advisory boards from AstraZeneca, Daiichi, BMS, Lilly, Servier. JF reports honoraria for lectures from Bayer and Servier, support for attending meetings from Bayer and Servier and participation in Advisory Boards for Servier. BS reports honoraria for lectures from Janssen and Servier. TP has received support for attending meetings and travel from IPSEN. ACA reports honoraria for lectures from MSD, AstraZeneca, IPSEN, Servier, Norvartis and Daiichi. PHD reports honoraria for lectures from AstraZeneca and Sanofi. AP reports honoraria for lectures from Servier, MSD, Zodiac, Amgen and AstraZeneca. FL reports that honoraria for lectures from Servier, BMS, MSD, Lilly, and AstraZeneca. She also reports support for attending meeting from AstraZeneca, BMS and Lilly and participation in advisory boards with Servier. MS reports honoraria for lectures from Servier and has received support for attending meetings and/or travel from IPSEN. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Immune checkpoints and their blockade. The blockade of CTLA-4 in the priming phase and the blockade of PD-1/PD-L1 in the effector phase. DC, dendritic cell; TCR, T-cell receptor; MHC, major histocompatibility complex; PD-1, programmed cell death-1; PD-L1, PD-ligand 1; CTLA-4, Cytotoxic T-lymphocyte–associated antigen-4. Figure generated with BioRender.
Figure 2
Figure 2
Gastric cancer microenvironment. The presence of different cell types in gastric cancer microenvironment and their role in the anti-tumor response. PD-L1, programmed cell death-ligand 1; CTLA-4, cytotoxic T-lymphocyte–associated antigen-4. Figure generated with BioRender.
See this image and copyright information in PMC

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