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Updated: Jan 27, 2026
Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
Published on: April 29, 2014
Harnessing the innate immune system and local immunological microenvironment to treat colorectal cancer
Jakob Nikolas Kather1,2,3, Niels Halama4,5,6,7
1Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
Abstract:
Significant progress in the development of new immunotherapies has led to successful clinical trials for malignant melanoma and non-small cell lung cancer; however, for the majority of solid tumours of the gastrointestinal tract, little or no progress has been seen. The efficacy of immunotherapies is limited by the complexities of a diverse set of immune cells, and interactions between the tumour cells and all other cells in the local microenvironment of solid tumours. A large fraction of immune cells present in and around solid tumours derive from the innate arm of the immune system and using these cells against tumours offers an alternative immunotherapeutic option, especially as current strategies largely harness the adaptive arm of the immune system. This option is currently being investigated and attempts at using the innate immune system for gastrointestinal cancers are showing initial results. Several important factors, including cytokines, chemotherapeutics and the microbiome, influence the plasticity and functionality of innate (myeloid) cells in the microenvironment, and this complexity of regulation has limited translation into successful trials so far. In this review, current concepts of the immunobiology of the innate arm in the tumour microenvironment are presented in the context of clinical translation.
Insights
Immunotherapies show promise for gastrointestinal cancers by targeting innate immune cells. Harnessing these cells offers a new strategy, overcoming limitations of current adaptive immune approaches for solid tumors.
Area of Science:
- Immunology
- Oncology
- Gastroenterology
Background:
- Immunotherapies have advanced treatments for melanoma and lung cancer but show limited success in gastrointestinal solid tumors.
- Tumor microenvironment complexity, involving diverse immune cells and cell interactions, impedes immunotherapy efficacy.
- Current immunotherapies primarily target the adaptive immune system, leaving the innate immune system largely untapped for solid tumors.
Purpose of the Study:
- To review the immunobiology of the innate immune system within the tumor microenvironment.
- To explore the potential of innate immune cells as a therapeutic target for gastrointestinal cancers.
- To discuss challenges and opportunities for translating innate immune strategies into clinical applications for solid tumors.
Main Methods:
- Literature review of current research on innate immunity in the tumor microenvironment.
- Analysis of factors influencing innate (myeloid) cell function, including cytokines, chemotherapeutics, and the microbiome.
- Examination of clinical trial data and preclinical studies related to innate immune-based therapies for gastrointestinal cancers.
Main Results:
- Innate immune cells constitute a significant portion of the immune infiltrate in solid tumors.
- Factors like cytokines, chemotherapeutics, and the microbiome critically regulate innate myeloid cell plasticity and function.
- Early investigations into utilizing the innate immune system for gastrointestinal cancers are yielding preliminary positive outcomes.
Conclusions:
- The innate immune system presents a promising alternative therapeutic avenue for gastrointestinal cancers.
- Understanding the complex regulatory network of innate cells in the tumor microenvironment is crucial for successful clinical translation.
- Further research and clinical trials are needed to fully harness the potential of innate immunotherapies for solid tumors.
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