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Updated: Mar 17, 2026
Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
Published on: June 7, 2018
Trial Watch-Small molecules targeting the immunological tumor microenvironment for cancer therapy
Aitziber Buqué1, Norma Bloy1, Fernando Aranda2
1INSERM, U1138, Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie/Paris VI, Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France; Gustave Roussy Cancer Campus, Villejuif, France.
Abstract:
Progressing malignancies establish robust immunosuppressive networks that operate both systemically and locally. In particular, as tumors escape immunosurveillance, they recruit increasing amounts of myeloid and lymphoid cells that exert pronounced immunosuppressive effects. These cells not only prevent the natural recognition of growing neoplasms by the immune system, but also inhibit anticancer immune responses elicited by chemo-, radio- and immuno therapeutic interventions. Throughout the past decade, multiple strategies have been devised to counteract the accumulation or activation of tumor-infiltrating immunosuppressive cells for therapeutic purposes. Here, we review recent preclinical and clinical advances on the use of small molecules that target the immunological tumor microenvironment for cancer therapy. These agents include inhibitors of indoleamine 2,3-dioxigenase 1 (IDO1), prostaglandin E2, and specific cytokine receptors, as well as modulators of intratumoral purinergic signaling and arginine metabolism.
Insights
Cancer progresses by creating immunosuppressive networks that hinder immune responses and therapies. Small molecules targeting these tumor microenvironment networks show promise for cancer treatment.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Progressing malignancies establish immunosuppressive networks systemically and locally.
- Tumors recruit immunosuppressive myeloid and lymphoid cells, hindering immune recognition and therapeutic responses.
- These cells inhibit natural anti-cancer immunity and responses to chemotherapy, radiotherapy, and immunotherapy.
Purpose of the Study:
- To review recent preclinical and clinical advances in using small molecules to target the immunological tumor microenvironment for cancer therapy.
- To discuss strategies counteracting immunosuppressive cells within tumors.
Main Methods:
- Review of preclinical and clinical studies.
- Focus on small molecule therapeutics targeting the tumor microenvironment.
- Analysis of agents inhibiting indoleamine 2,3-dioxigenase 1 (IDO1), prostaglandin E2, cytokine receptors, purinergic signaling, and arginine metabolism.
Main Results:
- Multiple strategies have been developed to counteract immunosuppressive cells in tumors.
- Small molecules targeting the tumor microenvironment are advancing in preclinical and clinical research.
- Specific agents include IDO1 inhibitors, prostaglandin E2 inhibitors, cytokine receptor modulators, and purinergic/arginine metabolism modulators.
Conclusions:
- Targeting the immunosuppressive tumor microenvironment with small molecules is a promising therapeutic strategy.
- Further research and clinical trials are essential to optimize these novel cancer therapies.
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