Related Experiment Video

Updated: Aug 20, 2026

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
07:44

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports

Published on: November 28, 2019

Reprogramming tumor-associated macrophages and interferon-gamma signaling to overcome therapeutic resistance in

HongMei Li1, Xiaoqiang Dai1

  • 1Xianyang Central Hospital, Xianyang 712000, China.

Pathology, Research and Practice
|August 18, 2026
PubMed

Insights

Tumor-associated macrophages (TAMs) drive cancer therapy resistance. Understanding TAM heterogeneity and interferon-gamma (IFN-γ) signaling is key to developing new strategies to overcome treatment evasion.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Biology

Background:

  • Therapeutic resistance is a significant challenge in cancer treatment, limiting the effectiveness of immunotherapies, chemotherapies, and targeted therapies.
  • Tumor-associated macrophages (TAMs) are key players in promoting this resistance through diverse mechanisms influenced by the tumor microenvironment.
  • Chronic exposure to interferon-gamma (IFN-γ) can further enhance adaptive resistance by modulating immune checkpoints and cellular metabolism.

Purpose of the Study:

  • To review the intersecting roles of TAM heterogeneity and IFN-γ signaling in promoting cancer therapy evasion.
  • To analyze the limitations of current TAM-targeting strategies and explore emerging therapeutic approaches.

Main Methods:

  • Literature review focusing on TAM heterogeneity, IFN-γ signaling, and therapeutic resistance mechanisms.
  • Analysis of preclinical and clinical data on TAM-directed therapies.
  • Evaluation of novel strategies including macrophage reprogramming and combination therapies.

Main Results:

  • TAM heterogeneity, influenced by factors like hypoxia and metabolic stress, contributes significantly to resistance.
  • IFN-γ signaling exacerbates resistance through checkpoint induction, metabolic rewiring, and epigenetic changes.
  • Many TAM-targeting strategies, such as CSF1R inhibition, show limited clinical efficacy compared to preclinical results.

Conclusions:

  • A deeper understanding of TAM states, spatial context, and IFN-γ dynamics is crucial for improving cancer treatment outcomes.
  • Developing biomarker-guided combination therapies and novel strategies like macrophage reprogramming holds promise for overcoming therapeutic resistance.
Keywords:
Interferon-γMacrophage ReprogrammingTherapeutic ResistanceTumor-Associated Macrophages

More Related Videos

Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion09:23

Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion

Published on: October 20, 2016

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.
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...