Abstract 3474
Background
Adoptive cell therapy (ACT) of expanded in-vitro tumour specific T-cells isolated from fresh tumour infiltrates has shown promising results in melanoma patients, and in ovarian cancer (OC). The use of pre-enriched tumor-specific T cells may simplify the TIL production method and enhances the tumour-reactivity of the final cellular product. We have investigated the role of PD-1 as a biomarker for the isolation and expansion of tumour-specific CD8 TILs in OC.
Methods
Samples from ten OC patients were analyzed. We used flow cytometry FACs Aria sorter for phenotyping and separate T-cells. For reactivity assay we performed co-cultures of TILs with autologous tumour and non-related tumor cell line, and measured INFγ released by ELISPOT. For immunofluorescence multiplex we used a Vectra® microscope and inForm® software to analyzed data. Tumour DNA sequencing was done using a TrueShight™ 170 gene panel.
Results
Both CD8+PD-1+and CD8+PD-1- TIL subsets expanded efficiently and no difference in fold expansion was found. Tumor-reactive TILs were detected in 5/10 patients and this tumor-reactivity was exclusively present in the cells derived from the PD-1+-enriched fraction. There were a higher frequency of CD8+PD-1+CD137+ by FC (p = 0,0079) in reactive group in fresh biopsy. Total CD8+and CD8+PD-1+were more frequent in reactive patients (p = 0,0079, p = 0,0317). CD8+PD-1+CD137+were more frequent (p = 0,0437) by IF in the tumoral epithelium of reactive patients. There were more total CD4+ and CD4+PD-1+by FC in reactive group (p = 0,0079, p = 0,0159). By IF we observed more CD4+PD-1+in both epithelium and stroma of reactive group (p = 0,0437). Patients with reactive TILs exhibited significantly high number of missense mutactions (p = 0,0198).
Conclusions
CD8+PD-1+ T-cell subset include tumour-specific T-cell in OC. CD8+PD-1+CD137+ cells in epithelium may work as a biomarker for reactivity. Higher mutation load is related with tumour-reactive TILs in OC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
ISCIII Spanish grant (PI15/02027).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4250 - Phase II study of avelumab in combination with cetuximab as a rechallenge strategy in pre-treated RAS wild type metastatic colorectal cancer patients: CAVE (cetuximab-avelumab) Colon.
Presenter: Erika Martinelli
Session: Poster Display session 2
Resources:
Abstract
5234 - The ORCHESTRA trial; A phase III trial of adding tumor debulking to systemic therapy versus systemic therapy alone in multi-organ metastatic colorectal cancer (mCRC).
Presenter: Lotte Bakkerus
Session: Poster Display session 2
Resources:
Abstract
5294 - EMERGE: Epigenetic Modulation of the Immune Response in Gastrointestinal cancers
Presenter: Elizabeth Cartwright
Session: Poster Display session 2
Resources:
Abstract
913 - Phase III, international, multicenter, randomized, open-label trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) alone for surgically resected pancreatic adenocarcinoma (APACT): subgroup analyses
Presenter: Margaret Tempero
Session: Poster Display session 2
Resources:
Abstract
1668 - FOLFIRINOX in locally advanced (LA) and borderline resectable (BR) pancreatic adenocarcinoma : update of the AGEO cohort.
Presenter: Edouard Auclin
Session: Poster Display session 2
Resources:
Abstract
2559 - Impact of adjuvant treatment with nab-paclitaxel and gemcitabine (nab-P+GEM) vs gemcitabine alone (GEM) on health-related quality of life (QoL) in patients (pts) with surgically resected pancreatic adenocarcinoma (PA) in the Adjuvant Pancreatic Adenocarcinoma Clinical Trial (APACT)
Presenter: Hanno Riess
Session: Poster Display session 2
Resources:
Abstract
4897 - Early detection of pancreatic ductal adenocarcinoma using methylation signatures in circulating tumor DNA
Presenter: Xiao-ding Liu
Session: Poster Display session 2
Resources:
Abstract
1755 - Evaluation of minimal important difference (MID) for the European Organisation for Research and Treatment of Cancer (EORTC) Pancreatic Cancer Module (PAN26) in patients with surgically resected pancreatic adenocarcinoma
Presenter: Michele Reni
Session: Poster Display session 2
Resources:
Abstract
2876 - Multispectral analysis of lymphocyte complexity in periampullary adenocarcinoma
Presenter: Sebastian Lundgren
Session: Poster Display session 2
Resources:
Abstract
1902 - Phase II trial of preoperative modified FOLFIRINOX (mFOLFIRINOX) followed by postoperative gemcitabine (GEM) in patients (pts) with borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC)
Presenter: Jae Ho Jeong
Session: Poster Display session 2
Resources:
Abstract