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.
