Mechanisms of Anti-PD Therapy Resistance in Digestive System Neoplasms

Title:Mechanisms of Anti-PD Therapy Resistance in Digestive System Neoplasms

Volume: 20 Issue: 1

Author(s): Yuxia Wu, Xiangyan Jiang, Zeyuan Yu*, Zongrui Xing, Yong Ma and Huiguo Qing

Affiliation:

• Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China

Keywords: Immunotherapy resistance, normalization cancer immunotherapy, PD-1/B7-H1, anti-PD-1/PD-L1 therapy, digestive system neoplasms, pancreatic cancer.

Abstract: Digestive system neoplasms are highly heterogeneous and exhibit complex resistance mechanisms that render anti-programmed cell death protein (PD) therapies poorly effective. The tumor microenvironment (TME) plays a pivotal role in tumor development, apart from supplying energy for tumor proliferation and impeding the body's anti-tumor immune response, the TME actively facilitates tumor progression and immune escape via diverse pathways, which include the modulation of heritable gene expression alterations and the intricate interplay with the gut microbiota. In this review, we aim to elucidate the mechanisms underlying drug resistance in digestive tumors, focusing on immune-mediated resistance, microbial crosstalk, metabolism, and epigenetics. We will highlight the unique characteristics of each digestive tumor and emphasize the significance of the tumor immune microenvironment (TIME). Furthermore, we will discuss the current therapeutic strategies that hold promise for combination with cancer immune normalization therapies. This review aims to provide a thorough understanding of the resistance mechanisms in digestive tumors and offer insights into potential therapeutic interventions.

Cite this article as:

Wu Yuxia, Jiang Xiangyan, Yu Zeyuan*, Xing Zongrui, Ma Yong and Qing Huiguo, Mechanisms of Anti-PD Therapy Resistance in Digestive System Neoplasms, Recent Patents on Anti-Cancer Drug Discovery 2025; 20 (1) . https://dx.doi.org/10.2174/0115748928269276231120103256