In patients with stage III or IV HGSOC who are not suitable for primary surgery (PDS), 3 cycles of platinum based NACT followed by interval surgery (IDS) and adjuvant chemotherapy is an accepted treatment approach. NACT enhances host immune response by increasing levels of PD1, CTLA4 and PDL1 (Böhm S et al. Clin Cancer Res 2016). Gene expression profiling of tumors has identified prognostic signatures for patient selection with immunotherapy (Ribas A et al. J Clin Oncol 2015).
The purpose of this study is to assess the effect of neoadjuvant chemotherapy (NACT) on immune activation in stage IIIC/IV tubo-ovarian high-grade serous carcinoma (HGSOC). We obtained pre- and post-treatment omental biopsies from a total of 45 patients undergoing platinum-based NACT followed by IDS. We measured T-cell density and phenotype, immune activation, and markers of cancer-related inflammation using IHC. Messenger RNA expression was analyzed on the nCounter system using the PanCancer IO360 Panel.
There was evidence of T-cell activation in omental biopsies after NACT. CD4+ T cells showed enhanced IFNgproduction and antitumor Th1 gene signatures were increased. T-cell activation correlated with therapeutic response to NACT. The CD8 T-cell and CD45RO memory cell density in the tumor microenvironment was unchanged after NACT, but biopsies after a good therapeutic response had significantly fewer FoxP3 + (Treg) cells. Biopsies of good therapeutic responders also showed areduction in a Treg gene signature in post versus pre-NACT samples.Preliminary results according to gene expression of the immune compartment reveal that tumor infiltrating lymphocytes were more abundant in samples from patients showing a good response over those with no or incomplete response to NACT, as well as an increase in gene signatures associated with antigen presentation and Cytokine and Chemokine Signaling. When comparing the expression profiles between samples obtained before or after NACT in patients showing incomplete response,we obtained an expected decreased in cellular proliferation signature.
NACT may promote an immune modulatory effect that could improve or favour the further use of specific immunotherapy in HGSOC patients.
Fundación para la Investigación 12 de Octubre.
Tesaro SL.
L.M. Manso: Research grant / Funding (self): Tesaro; Advisory / Consultancy: Roche, Novartis, Tesaro, AstraZeneca, Pfizer, Clovis; Speaker Bureau / Expert testimony: Roche, Novartis, Tesaro, AstraZeneca, Pfizer, Clovis; Travel / Accommodation / Expenses: Roche, Novartis, Tesaro, Pfizer. S. Wang: Full / Part-time employment: Tesaro. All other authors have declared no conflicts of interest.