Systemic Interferon-g Increases MHC Class I Expression and T-cell Infiltration in Cold Tumors: Results of a phase 0 clinical trial

Shihong Zhang, Karan Kohli, R. Graeme Black, Lu Yao, Sydney M. Spadinger, Qianchuan He, Venu G. Pillarisetty, Lee D Cranmer, Brian A. Van Tine, Cassian Yee, Robert H. Pierce, Stanley R. Riddell, Robin L. Jones, Seth M. Pollack

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1237-1243
Number of pages7
JournalCancer Immunology Research
Volume7
Issue number8
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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    Zhang, S., Kohli, K., Graeme Black, R., Yao, L., Spadinger, S. M., He, Q., Pillarisetty, V. G., Cranmer, L. D., Van Tine, B. A., Yee, C., Pierce, R. H., Riddell, S. R., Jones, R. L., & Pollack, S. M. (2019). Systemic Interferon-g Increases MHC Class I Expression and T-cell Infiltration in Cold Tumors: Results of a phase 0 clinical trial. Cancer Immunology Research, 7(8), 1237-1243. https://doi.org/10.1158/2326-6066.CIR-18-0940