Related Experiment Video

Updated: Aug 5, 2026

Co-Culture In Vitro Systems to Reproduce the Cancer-Immunity Cycle
12:19

Co-Culture In Vitro Systems to Reproduce the Cancer-Immunity Cycle

Published on: June 7, 2024

Tumor cell-released autophagosome (TRAP) programs inflammatory CAFs to drive the immune-excluded TIME through C3a

Xuru Wang1,2, Yiting Wei1, Chengdong Wu1

  • 1Department of Microbiology and Immunology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.

Cellular & Molecular Immunology
|July 29, 2026
PubMed

Insights

Tumor cells release autophagosomes (TRAP) that program cancer-associated fibroblasts (CAFs) to suppress anti-tumor immunity. Targeting this TRAP-CAF-C3a pathway can remodel the tumor microenvironment and improve immunotherapy response.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • The immune-excluded tumor immune microenvironment (TIME) hinders responses to immune checkpoint inhibitors (ICIs).
  • Cancer-associated fibroblasts (CAFs) are key regulators of immune suppression within the TIME, but the signals that program their pathogenic states are unclear.

Purpose of the Study:

  • To define the upstream cues and mechanisms driving immune exclusion in the TIME.
  • To investigate the role of tumor cell-released autophagosomes (TRAP) in programming CAFs and shaping the TIME.

Main Methods:

  • Single-cell RNA sequencing to identify cellular interactions and pathways.
  • Functional validation experiments to confirm molecular mechanisms.
  • Analysis of clinical cohorts to assess biomarker potential.

Main Results:

  • Tumor cell-released autophagosomes (TRAP) program inflammatory CAFs (iCAFs).
  • iCAFs, via cathepsin L and the HSP70-TLR4-MyD88-ERK/p38 pathway, generate C3a, which attracts TAMs and limits T cell infiltration, reinforcing immune exclusion.
  • Disrupting the TRAP-iCAF-C3a axis remodels the TIME and sensitizes tumors to anti-PD-L1 therapy.
  • Plasma TRAP and C3a levels correlate with disease stage and can discriminate breast cancer patients from controls.

Conclusions:

  • A TRAP-driven stromal-immune circuit promotes immune exclusion.
  • The C3a-C3aR axis is a potential therapeutic target for enhancing ICI efficacy in cancer.
Keywords:
C3aCTSLImmune-excluded tumor immune microenvironment (TIME)Inflammatory CAFsTumor cell-released autophagosome (TRAP)

More Related Videos

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity06:16

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity

Published on: December 7, 2019

Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies09:01

Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies

Published on: July 3, 2025

Related Concept Videos

Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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.
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...