Novel immunotherapeutic approaches in gastric cancer

Abstract

Gastric cancer is a malignant tumor that ranks third in cancer-related deaths worldwide. Early-stage gastric cancer can often be effectively managed through surgical resection. However, the majority of cases are diagnosed in advanced stages, where outcomes with conventional radiotherapy and chemotherapy remain unsatisfactory. Immunotherapy offers a novel approach to treating molecularly heterogeneous gastric cancer by modifying the immunosuppressive tumor microenvironment. Immune checkpoint inhibitors and adoptive cell therapy are regarded as promising modalities in cancer immunotherapy. Food and Drug Administration-approved programmed death-receptor inhibitors, such as pembrolizumab, in combination with chemotherapy, have significantly extended overall survival in gastric cancer patients and is recommended as a first-line treatment. Despite challenges in solid tumor applications, adoptive cell therapy has demonstrated efficacy against various targets in gastric cancer treatment. Among these approaches, chimeric antigen receptor-T cell therapy research is the most widely explored and chimeric antigen receptor-T cell therapy targeting claudin18.2 has shown acceptable safety and robust anti-tumor capabilities. However, these advancements primarily remain in preclinical stages and further investigation should be made to promote their clinical application. This review summarizes the latest research on immune checkpoint inhibitors and adoptive cell therapy and their limitations, as well as the role of nanoparticles in enhancing immunotherapy.

Keywords

gastric cancer / immunotherapy / immune checkpoint inhibitor / adoptive cell therapy / CAR-T

Acknowledgements

This research was supported by the National Key Research and Development Program of China (Grant No. 2021YFF1201300), the National Natural Science Foundation of China (Grants No. 82273402, 92374114, and 81930065), the Science and Technology Program of Guangdong (Grant No. 2019B020227002), the Natural Science Foundation of Guangdong Province (Grant No. 2014A030312015), the Science and Technology Program of Guangzhou (Grants No. 202002030208, 201904020046, and 2019B020227002), Guangzhou Key Research and Development Project (Grant No. 202206080008), and Guangdong Special Support Plan (Grant No. 2023TX07Y430).

Author contributions

H.Y.L.: conceptualization, supervision, project administration, funding acquisition. W.H.L., M.Y., J.Q.H.: data curation, software, formal analysis, investigation, visualization, methodology. H.Y.L., W.H.L., M.Y., J.Q.H., A.M.: Writing - original draft, writing - review and editing. All the authors reviewed and approved the final manuscript.

Conflict of interest

None declared. As an Editorial Board Member of Precision Clinical Medicine, the corresponding author H.Y.L. was blinded from reviewing and making decisions on this manuscript.

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