Details

Autor(en) / Beteiligte

• Lo, Charlotte S
• Sanii, Sanaz
• Kroeger, David R
• Milne, Katy
• Talhouk, Aline
• Chiu, Derek S
• Rahimi, Kurosh
• Shaw, Patricia A
• Clarke, Blaise A
• Nelson, Brad H

Titel

Neoadjuvant Chemotherapy of Ovarian Cancer Results in Three Patterns of Tumor-Infiltrating Lymphocyte Response with Distinct Implications for Immunotherapy

Ist Teil von

• Clinical cancer research, 2017-02, Vol.23 (4), p.925-934

Ort / Verlag

United States: American Association for Cancer Research Inc

Erscheinungsjahr

2017

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Some forms of chemotherapy can enhance antitumor immunity through immunogenic cell death, resulting in increased T-cell activation and tumor infiltration. Such effects could potentially sensitize tumors to immunotherapies, including checkpoint blockade. We investigated whether platinum- and taxane-based chemotherapy for ovarian cancer induces immunologic changes consistent with this possibility. Matched pre- and post-neoadjuvant chemotherapy tumor samples from 26 high-grade serous carcinoma (HGSC) patients were analyzed by immunohistochemistry (IHC) for a large panel of immune cells and associated factors. The prognostic significance of post-chemotherapy TIL patterns was assessed in an expanded cohort ( = 90). Neoadjuvant chemotherapy was associated with increased densities of CD3 , CD8 , CD8 TIA-1 , PD-1 and CD20 TIL. Other immune subsets and factors were unchanged, including CD79a CD138 plasma cells, CD68 macrophages, and MHC class I on tumor cells. Immunosuppressive cell types were also unchanged, including FoxP3 PD-1 cells (putative regulatory T cells), IDO-1 cells, and PD-L1 cells (both macrophages and tumor cells). Hierarchical clustering revealed three response patterns: (i) TIL tumors showed increases in multiple immune markers after chemotherapy; (ii) TIL tumors underwent similar increases, achieving patterns indistinguishable from the first group; and (iii) TIL cases generally remained negative. Despite the dramatic increases seen in the first two patterns, post-chemotherapy TIL showed limited prognostic significance. Chemotherapy augments pre-existing TIL responses but fails to relieve major immune-suppressive mechanisms or confer significant prognostic benefit. Our findings provide rationale for multipronged approaches to immunotherapy tailored to the baseline features of the tumor microenvironment. .