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Tumor Immunotherapy

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 Microenvironment

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...

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Updated: May 9, 2025

Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors

Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors

Published on: June 7, 2018

Single-cell transcriptomic analysis reveals gut microbiota-immunotherapy synergy through modulating tumor

Minyuan Cao^1,2, Yun Deng², Qing Hao²

¹Department of Laboratory Medicine/Research Centre of Clinical Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Signal Transduction and Targeted Therapy

|May 1, 2025

Summary

The gut microbiota enhances immune checkpoint inhibitor (ICI) immunotherapy by boosting T cell responses and reprogramming tumor-associated macrophages (TAMs). This synergy involves a γδ T cell-APC-CD8+ T cell axis, improving antitumor immunity.

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Last Updated: May 9, 2025

Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors

Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors

Published on: June 7, 2018

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Published on: April 30, 2021

Predictive Immune Modeling of Solid Tumors

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Published on: February 25, 2020

Area of Science:

Immunology
Microbiology
Cancer Research

Background:

Immune checkpoint inhibitors (ICIs) are vital cancer therapies, but their efficacy is influenced by the gut microbiota.
The precise single-cell mechanisms underlying gut microbiota-ICI synergy remain largely unknown.
Understanding these mechanisms is crucial for optimizing immunotherapy outcomes.

Purpose of the Study:

To investigate the synergistic effects of gut microbiota and ICIs on the tumor microenvironment (TME) at a single-cell level.
To elucidate the cellular interactions and molecular pathways involved in this synergy.
To identify potential therapeutic targets for enhancing immunotherapy.

Main Methods:

Single-cell RNA sequencing (scRNA-seq) of the TME in mouse models.
Validation studies including fecal microbiota transplantation and genetic depletion of specific cell populations (Spp1+ TAMs).
Analysis of cellular interactions, metabolic pathways, and signaling cascades (e.g., NF-κB).

Main Results:

Combined gut microbiota and ICIs increased CD8+, CD4+, and γδ T cells, reduced glycolysis, and reversed CD8+ T cell exhaustion.
Macrophage reprogramming occurred from M2 Spp1+ TAMs to Cd74+ APCs, with a negative correlation between these subtypes.
Depletion of Spp1+ TAMs enhanced ICI efficacy and T cell infiltration, irrespective of microbiota status.
A proposed γδ T cell-APC-CD8+ T cell axis mediated synergy via CD40-CD40L and CD86-CD28 interactions.

Conclusions:

Gut microbiota and ICIs synergistically enhance antitumor responses by modulating TME cellular composition and function.
Spp1+ TAMs negatively impact immunotherapy, while Cd74+ TAMs may act as beneficial APCs.
Targeting the γδ T cell-APC-CD8+ T cell axis and macrophage reprogramming presents a promising strategy for improving ICI therapy.