Related Experiment Video

Updated: Aug 6, 2026

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
07:36

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

Published on: June 12, 2021

Breaking immune exclusion in cold tumors via TGF-β pathway inhibition

Minjun Zhang1, Yuchen Sun1, Luyan Chen1

  • 1Department of Breast Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.

Expert Opinion on Biological Therapy
|July 24, 2026
PubMed
Abstract

Insights

Transforming cold tumors requires overcoming immune exclusion driven by TGF-β. Dual targeting of TGF-β and PD-(L)1 shows promise but needs biomarker-guided strategies for success.

Area of Science:

  • Oncology
  • Immunotherapy
  • Cancer Biology

Background:

  • Immune exclusion in cold tumors is a primary driver of immunotherapy resistance.
  • Transforming growth factor-beta (TGF-β) signaling is a key regulator of this immune-suppressive tumor microenvironment.
  • The development of dual-targeting agents combining TGF-β and PD-(L)1 blockade presents a promising therapeutic strategy.

Purpose of the Study:

  • To critically examine the mechanisms by which TGF-β contributes to immune exclusion.
  • To analyze preclinical and clinical data on TGF-β/PD-(L)1 dual-targeting agents.
  • To discuss translational challenges and future directions for this therapeutic approach.

Main Methods:

  • Systematic review of preclinical and clinical evidence on TGF-β/PD-(L)1 dual blockade.
  • Literature search of PubMed and major oncology conference proceedings.
  • Analysis of bifunctional fusion proteins (e.g., M7824, SHR-1701) and bispecific antibodies.

Main Results:

  • TGF-β drives immune exclusion via stromal remodeling, metabolic suppression, and immune cell regulation.
  • Dual-targeting agents have demonstrated both setbacks and breakthroughs in clinical development.
  • Key challenges include defining the therapeutic window, developing predictive biomarkers, and selecting appropriate indications.

Conclusions:

  • Successful TGF-β-targeted therapy necessitates biomarker-guided patient selection and context-specific interventions.
  • Future clinical development will likely involve spatially or biologically restricted targeting, multi-parametric biomarkers, and mechanism-based combination therapies.
Keywords:
Cancer immunotherapyPD-1/PD-L1TGF-βcold tumorimmune exclusion

More Related Videos

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells09:04

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells

Published on: March 7, 2025

Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...