Translating Knowledge About the Immune Microenvironment of Gastrointestinal Stromal Tumors into Effective Clinical Strategies

Jomjit Chantharasamee^{1

2}, Jacob J Adashek³, Karlton Wong¹, Mark A Eckardt^{4

5}, Bartosz Chmielowski^{1

6}, Sarah Dry^{6

7}, Fritz C Eilber^{5

6}, Arun S Singh^{8

9}

Affiliations

¹ Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, CA, USA.
² Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
³ Department of Internal Medicine, University of South Florida, H. Lee Moffit Cancer Center, Tampa, FL, USA.
⁴ Department of Surgery, Yale School of Medicine, New Haven, CT, USA.
⁵ Division of Surgical Oncology, University of California Los Angeles, Los Angeles, CA, USA.
⁶ UCLA-JCCC Sarcoma Program, Los Angeles, CA, USA.
⁷ Department of Pathology, University of California Los Angeles, Los Angeles, CA, USA.
⁸ Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, CA, USA. asingh@mednet.ucla.edu.
⁹ Department of Pathology, University of California Los Angeles, Los Angeles, CA, USA. asingh@mednet.ucla.edu.

PMID: 33400014
DOI: 10.1007/s11864-020-00806-z

Review

Translating Knowledge About the Immune Microenvironment of Gastrointestinal Stromal Tumors into Effective Clinical Strategies

Jomjit Chantharasamee et al. Curr Treat Options Oncol. 2021.

. 2021 Jan 5;22(1):9.

doi: 10.1007/s11864-020-00806-z.

Authors

Jomjit Chantharasamee^{1

2}, Jacob J Adashek³, Karlton Wong¹, Mark A Eckardt^{4

5}, Bartosz Chmielowski^{1

6}, Sarah Dry^{6

7}, Fritz C Eilber^{5

6}, Arun S Singh^{8

9}

Affiliations

¹ Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, CA, USA.
² Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
³ Department of Internal Medicine, University of South Florida, H. Lee Moffit Cancer Center, Tampa, FL, USA.
⁴ Department of Surgery, Yale School of Medicine, New Haven, CT, USA.
⁵ Division of Surgical Oncology, University of California Los Angeles, Los Angeles, CA, USA.
⁶ UCLA-JCCC Sarcoma Program, Los Angeles, CA, USA.
⁷ Department of Pathology, University of California Los Angeles, Los Angeles, CA, USA.
⁸ Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, CA, USA. asingh@mednet.ucla.edu.
⁹ Department of Pathology, University of California Los Angeles, Los Angeles, CA, USA. asingh@mednet.ucla.edu.

PMID: 33400014
DOI: 10.1007/s11864-020-00806-z

Abstract

The role of targeted therapy is firmly established for gastrointestinal stromal tumors (GISTs); other modalities for targeting this disease are necessary for recurrent and refractory disease. There are several lines of evidence pointing to an active role of the immune system in GIST. Preclinical and clinical studies revealed that the most common type of immune cell infiltration in GISTs is tumor-associated macrophages (TAMs). The mechanism of how TAMs sculpt the tumor microenvironment in GIST is not clear, but it seems that the presence of immunosuppressive regulatory T cells (Tregs) is correlated with the number of TAMs, thus linking macrophages to immunosuppression. CD3+ T cells and NK infiltrates are found in the GIST microenvironment and carry some prognostic value. In early clinical trials, there is evidence for an active role for immunotherapy in treating GIST patients. Moreover, preclinical evidence has indicated that combining TKIs with checkpoint blockers may be synergistic in murine GIST models. Overall, there is substantial preclinical and clinical evidence to support a role for immunoregulation in GIST and further studies will be important for the development of immunotherapies for GIST.

Keywords: Cancer clinical trials; Gastrointestinal stromal tumors; Immune checkpoint inhibitors; Immunotherapy.

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References

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

1. Judson I, Demetri G. Advances in the treatment of gastrointestinal stromal tumours. Ann Oncol. 2007;18(Suppl 10):x20–4. - PubMed - DOI - PMC
1. Corless CL, Heinrich MC. Molecular pathobiology of gastrointestinal stromal sarcomas. Annu Rev Pathol. 2008;3:557–86. - PubMed - DOI - PMC
1. Watson GA, Kelly D, Melland-Smith M, Gleeson J, McEntee G, Kelly CM, et al. Get the GIST? An overview of gastrointestinal stromal tumours. Ir J Med Sci. 2016;185(2):319–26. - PubMed - DOI - PMC
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Translating Knowledge About the Immune Microenvironment of Gastrointestinal Stromal Tumors into Effective Clinical Strategies

Affiliations

Translating Knowledge About the Immune Microenvironment of Gastrointestinal Stromal Tumors into Effective Clinical Strategies

Authors

Affiliations

Abstract

References

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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LinkOut - more resources

Full Text Sources

Other Literature Sources