TY - JOUR
T1 - Systemic Interferon-g Increases MHC Class I Expression and T-cell Infiltration in Cold Tumors
T2 - Results of a phase 0 clinical trial
AU - Zhang, Shihong
AU - Kohli, Karan
AU - Graeme Black, R.
AU - Yao, Lu
AU - Spadinger, Sydney M.
AU - He, Qianchuan
AU - Pillarisetty, Venu G.
AU - Cranmer, Lee D.
AU - Van Tine, Brian A.
AU - Yee, Cassian
AU - Pierce, Robert H.
AU - Riddell, Stanley R.
AU - Jones, Robin L.
AU - Pollack, Seth M.
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85070489386&partnerID=8YFLogxK
U2 - 10.1158/2326-6066.CIR-18-0940
DO - 10.1158/2326-6066.CIR-18-0940
M3 - Article
C2 - 31171504
AN - SCOPUS:85070489386
SN - 2326-6066
VL - 7
SP - 1237
EP - 1243
JO - Cancer immunology research
JF - Cancer immunology research
IS - 8
ER -