Format

Send to

Choose Destination
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.

Author information

1
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
2
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
3
Department of Surgery, University of Washington, Seattle, Washington.
4
Division of Medical Oncology, University of Washington, Seattle, Washington.
5
Division of Oncology, Washington University in St. Louis, St. Louis, Missouri.
6
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
7
Sarcoma Unit, Royal Marsden Hospital and Institute of Cancer Research, London, UK.
8
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. spollack@fredhutch.org.

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.

PMID:
31171504
PMCID:
PMC6677581
[Available on 2020-02-01]
DOI:
10.1158/2326-6066.CIR-18-0940

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center