Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Aug 19;22(1):405.
doi: 10.1186/s12964-024-01776-7.

The complex interplay of tumor-infiltrating cells in driving therapeutic resistance pathways

Dengxiong Li #  1 , Fanglin Shao #  2 , Qingxin Yu #  3   4 , Ruicheng Wu #  1 , Zhouting Tuo  5 , Jie Wang  1 , Luxia Ye  6 , Yiqing Guo  6 , Koo Han Yoo  7 , Mang Ke  6   8 , Uzoamaka Adaobi Okoli  9   10 , Chaipanichkul Premkamon  9 , Yubo Yang  11 , Wuran Wei  12 , Susan Heavey  13 , William C Cho  14 , Dechao Feng  15   16
Affiliations
Review

The complex interplay of tumor-infiltrating cells in driving therapeutic resistance pathways

Dengxiong Li et al. Cell Commun Signal. .

Abstract

Drug resistance remains a significant challenge in cancer treatment. Recently, the interactions among various cell types within the tumor microenvironment (TME) have deepened our understanding of the mechanisms behind treatment resistance. Therefore, this review aims to synthesize current research focusing on infiltrating cells and drug resistance suggesting that targeting the TME could be a viable strategy to combat this issue. Numerous factors, including inflammation, metabolism, senescence, hypoxia, and angiogenesis, contribute to drug resistance could be a viable strategy to combat this issue. Overexpression of STAT3 is commonly associated with drug-resistant cancer cells or stromal cells. Current research often generalizes the impact of stromal cells on resistance, lacking specificity and statistical robustness. Thus, future research should take notice of this issue and aim to provide high-quality evidence. Despite the existing limitations, targeting the TME to overcome therapy resistance hold promising and valuable potential.

Keywords: Drug resistance; Immunotherapy; Infiltrated cells; Radiotherapy; Targeted therapy; Tumor microenvironment.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The evolution of infiltration cells contributes to immunotherapy resistance. Exhibiting the interaction between various infiltration cells in tumor microenvironment. Various factors promoted the formation of immunotherapy resistance microenvironment, such as EMT activation, angiogenesis, and metabolism reprogramming. EMT. Tregs: regulatory T cells; MDSC: myeloid-derived suppressor cell; EMT: Epithelial–mesenchymal transition
Fig. 2
Fig. 2
The evolution of infiltration cells contributes to resistance against targeted therapy. The picture specifically describes how different cells (including immune and non-immune cells) generate a therapy-resistant microenvironment via CD4 + and CD8 + T cells inhibition, activating and recruiting regulatory T Cells, and angiogenesis upregulation. MDSC: myeloid-derived suppressor cell; Treg: regulatory T cell; ROS: reactive oxygen species; TAM: Tumor-associated macrophage
Fig. 3
Fig. 3
Chemotherapy-induced hypoxia, vascular damage, and chronic inflammation are associated with the development of chemoresistance. Various infiltration cells in the TME play crucial roles in contributing to chemoresistance. Various factors promoted the formation of chemoresistance microenvironment, such as STAT3 pathway activation, EMT activation, and TAFs secreted pro-tumor exosomes. MDSCs: myeloid-derived suppressor cell; Tregs: regulatory T cells; MSCs: mesenchymal stem cells; BMSCs: bone marrow stromal cells; TAFs: Tumor-associated fibroblasts.; TAM: Tumor-associated macrophage
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Gao YY, Yang WC, Ashby CR Jr., Hao GF. Mapping cryptic binding sites of drug targets to overcome drug resistance. Drug Resist Updates: Reviews Commentaries Antimicrob Anticancer Chemother. 2023;67:100934.10.1016/j.drup.2023.100934 - DOI - PubMed
    1. Li D, Yu Q, Wu R, Tuo Z, Zhu W, Wang J et al. Chronobiology of the Tumor Microenvironment: implications for therapeutic strategies and circadian-based interventions. Aging Dis 2024. - PubMed
    1. Li D, Wang J, Tuo Z, Yoo KH, Yu Q, Miyamoto A et al. Natural products and derivatives in renal, urothelial and testicular cancers: targeting signaling pathways and therapeutic potential. Phytomedicine: international journal of phytotherapy and phytopharmacology 2024. - PubMed
    1. Cerella C, Dicato M, Diederich M. Enhancing personalized immune checkpoint therapy by immune archetyping and pharmacological targeting. Pharmacol Res. 2023;196:106914. 10.1016/j.phrs.2023.106914 - DOI - PubMed
    1. Gottesman MM, Robey RW, Ambudkar SV. New mechanisms of multidrug resistance: an introduction to the Cancer Drug Resistance special collection. Cancer Drug Resist. 2023;6:590–5. 10.20517/cdr.2023.86 - DOI - PMC - PubMed

LinkOut - more resources