Therapeutic Strategies for Targeting TAFs in TME

Relying on the technology platform of the tumor microenvironment center, Alfa Cytology offers a full range of solutions and services or strategies for investigating therapeutic strategies that for target TAFs in the tumor microenvironment (TME), helping researchers successfully achieve their research goals.

Introduction

The tumor microenvironment (TME) supports the development of tumors by acting as a "soil". Tumor-associated fibroblasts (TAFs) are the main stromal cells in the tumor microenvironment and play an important role in the regulation of the tumor vascular network, outer stroma and other stromal cells. TAFs can suppress the function of immune cells by secreting various cytokines/metabolites and promote tumor development, invasion, metastasis, and drug resistance. The extracellular matrix produced by TAFs can also limit the efficacy of tumor therapy. Therefore, TAFs have become a new target for tumor therapy, and inhibiting tumor progression by targeting and modulating TAFs or overcoming their barrier effects is a new means to improve the efficacy of tumor therapy.

Fig. 1 Mechanisms of tumor progress promoted by cancer-associated fibroblasts (CAFs). CAFs inhibits immune cells penetration, suppress immune cell ability and promotes tumor development by secreting cytokines, extracellular matrix (ECM) production and metabolism substances secretion. (YUAN Shi-jun, et al., 2015)

IL-6: Interleukin-6; SDF-1: Stromal cell-derived factor-1; CCL2: C-C motif chemokine ligand 2; M-CSF: Macrophage colony-stimulating factor; TGF-β: Transforming growth factor-β; PGE2: Prostaglandin E2; IDO: Indoleamine 2,3-dioxygenase; VEGF: Vascular endothelial growth factor; PD-L2: Programmed death ligand 2; MMP: Matrix metalloproteinase; TME: Tumor microenvironment; MDSC: Myeloid-derived suppressor cells; TAM: Tumor-associated macrophages; NK: Natural killer.

Solutions

TAFs, as a major class of stromal cells in tumor tissues, have a role in promoting tumor progression. Therefore, tumor treatment strategies that target and modulate TAFs are expected to inhibit tumor progression. However, traditional drug delivery strategies still suffer from insufficient drug distribution specificity and systemic toxicity, thus limiting the development of this new strategy for tumor treatment.

Alfa Cytology has established an innovative tumor microenvironment center technology platform and is developing several technologies designed to help global collaborators develop therapeutic strategies targeting tumor-associated fibroblasts (TAFs) in tumor microenvironment (TME). We are developing new therapeutic strategies for tumor treatment, and nanocarriers, with their targeted delivery capability, controlled drug release and good biocompatibility, can be used in targeted modulation of TAFs therapeutic strategies to enhance drug accumulation at target sites, increase tolerated dose and enhance therapeutic efficacy.

Key strategies

Currently, Alfa Cytology focuses on three main therapeutic strategies for targeted modulation of TAFs, including killing TAFs, interfering with the function of TAFs and interfering with the activation of TAFs.

Killing TAFs

It mainly uses nanocarriers to deliver cytotoxic drugs or vaccines to TAFs with high efficiency to achieve selective killing of TAFs, alleviate the tumor suppressive microenvironment, increase the penetration of anti-tumor drugs, and promote the activation and infiltration of immune cells.

Interfering with the function of TAFs

It reduces the secretion of cytokines by TAFs through the delivery of cytokine antagonists and anti-fibrotic drugs, thus blocking the intercellular information exchange and effectively weakening the tumor-promoting effect of TAFs.

Interfering with the activation of TAFs

It mainly refers to the process of transformation of static fibroblasts and stellate cells into an activated phenotype with activation markers that can secrete collagen and cytokines under the action of stimulating factors such as TGF-B/PDGF secreted by tumors.

Note: The key strategies we focus on are always up to date, please contact us by email for more up-to-date and relevant information.

Alfa Cytology is committed to supporting scientists in making breakthrough scientific discoveries and developing new applications to accelerate new drug discovery and scientific diagnosis and treatment. Our high-performance scientific instruments and high-value solutions enable scientists to explore the mysteries of life at the tumor microenvironment level. Please tell us your project requirements, and we will provide you with a full service from solution to report. If you have any questions, please feel free to contact us.

Reference

YUAN Shi-jun, LIU Yong-jun*, ZHANG Na*. Recent advances on cancer-associated fibroblasts treatment strategies and delivery systems[J]. Acta Pharmaceutica Sinica, 2022, 57(3): 638-643.

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