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Cancer Immunol Res. 2019 Aug;7(8):1237-1243. doi: 10.1158/2326-6066.CIR-18-0940. Epub 2019 Jun 6.

Systemic Interferon-γ Increases MHC Class I Expression and T-cell Infiltration in Cold Tumors: Results of a Phase 0 Clinical Trial.

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Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Department of Surgery, University of Washington, Seattle, Washington.
Division of Medical Oncology, University of Washington, Seattle, Washington.
Division of Oncology, Washington University in St. Louis, St. Louis, Missouri.
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Sarcoma Unit, Royal Marsden Hospital and Institute of Cancer Research, London, UK.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.


Interferon-γ (IFNγ) has been studied as a cancer treatment with limited evidence of clinical benefit. However, it could play a role in cancer immunotherapy combination treatments. Despite high expression of immunogenic cancer-testis antigens, synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) have a cold tumor microenvironment (TME), with few infiltrating T cells and low expression of major histocompatibility complex class I (MHC-I). We hypothesized that IFNγ treatment could drive inflammation in a cold TME, facilitating further immunotherapy. We conducted a phase 0 clinical trial treating 8 SS or MRCL patients with weekly systemic IFNγ. We performed pre- and posttreatment biopsies. IFNγ changed the SS and MRCL TME, inducing tumor-surface MHC-I expression and significant T-cell infiltration (P < 0.05). Gene-expression analysis suggested increased tumor antigen presentation and less exhausted phenotypes of the tumor-infiltrating T cells. Newly emergent antigen-specific humoral and/or T-cell responses were found in 3 of 7 evaluable patients. However, increased expression of PD-L1 was observed on tumor-infiltrating myeloid cells and in some cases tumor cells. These findings suggest that systemic IFNγ used to convert SS and MRCL into "hot" tumors will work in concert with anti-PD-1 therapy to provide patient benefit.

[Available on 2020-02-01]

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