Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
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
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.
.