Effector T Cells Abrogate Stroma-Mediated Chemoresistance in Ovarian Cancer | Zendy

Weimin Wang | Zendy; Ilona Kryczek | Zendy; Lubomír Dostál | Zendy; Heng Lin | Zendy; Lijun Tan | Zendy; Lili Zhao | Zendy; Fujia Lu | Zendy; Shuang Wei | Zendy; Tomasz Maj | Zendy; Dongjun Peng | Zendy; He Gong | Zendy; Linda Vatan | Zendy; Wojciech Szeliga | Zendy; Rork Kuick | Zendy; Jan Kotarski | Zendy; Rafał Tarkowski | Zendy; Yali Dou | Zendy; Ramandeep Rattan | Zendy; Adnan Munkarah | Zendy; J. Rebecca Liu | Zendy; Weiping Zou | Zendy

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Effector T Cells Abrogate Stroma-Mediated Chemoresistance in Ovarian Cancer

Author(s) -

Weimin Wang,

Ilona Kryczek,

Lubomír Dostál,

Heng Lin,

Lijun Tan,

Lili Zhao,

Fujia Lu,

Shuang Wei,

Tomasz Maj,

Dongjun Peng,

He Gong,

Linda Vatan,

Wojciech Szeliga,

Rork Kuick,

Jan Kotarski,

Rafał Tarkowski,

Yali Dou,

Ramandeep Rattan,

Adnan Munkarah,

J. Rebecca Liu,

Weiping Zou

Publication year - 2016

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2016.04.009

Subject(s) - biology , cytotoxic t cell , stromal cell , glutathione , cancer research , cd8 , cancer cell , microbiology and biotechnology , tumor microenvironment , effector , cancer , immunology , immune system , biochemistry , in vitro , genetics , tumor cells , enzyme

Effector T cells and fibroblasts are major components in the tumor microenvironment. The means through which these cellular interactions affect chemoresistance is unclear. Here, we show that fibroblasts diminish nuclear accumulation of platinum in ovarian cancer cells, resulting in resistance to platinum-based chemotherapy. We demonstrate that glutathione and cysteine released by fibroblasts contribute to this resistance. CD8(+) T cells abolish the resistance by altering glutathione and cystine metabolism in fibroblasts. CD8(+) T-cell-derived interferon (IFN)γ controls fibroblast glutathione and cysteine through upregulation of gamma-glutamyltransferases and transcriptional repression of system xc(-) cystine and glutamate antiporter via the JAK/STAT1 pathway. The presence of stromal fibroblasts and CD8(+) T cells is negatively and positively associated with ovarian cancer patient survival, respectively. Thus, our work uncovers a mode of action for effector T cells: they abrogate stromal-mediated chemoresistance. Capitalizing upon the interplay between chemotherapy and immunotherapy holds high potential for cancer treatment.

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