Abstract 2439
Background
Tumour infiltrating T cell subsets are associated with a prognosis in gastric cancer (GC). However, there has been no study of T cell subsets on the efficacy of immune checkpoint blockades (ICBs). This study was designed to assess T cell subsets in tumour by using multiplex immunohistochemistry (mIHC) and to evaluate the association of T cell subsets and efficacy of ICBs in patients with GC who received ICBs.
Methods
We assess patients who have treated with ICBs and available tumour tissues before initiation of ICBs. Multiple stainings were performed with different kinds of T cell or immune checkpoint surface markers (CD3, CD4, CD8, PD-L1, PD1, FOXP3, CK, Ki-67, TIM-3, LAG-3, CD45 and CD45RO) in a single section through 12 times-repeated staining-scanning-stripping procedures. Density was defined to be the number of positively-stained cells per mm2.
Results
Eighty-four patients (40 (47.6%) in first- or second-line; 44 (52.4%) in third- or later lines) were analyzed. Patients with MSI-H, EBV and non-MSI/non-EBV were 7 (8.3%), 3 (3.6%) and 74 (88.1%). A high intratumoral CD3+CD8+/CD3+ T cells ratio was associated with better response rate (RR) (34.2% vs 8.8%, p = 0.034) and longer overall survival (OS) (24.3 vs. 5.9 months, p < 0.001). A high CD3+CD8+ density (17.9 vs. 5.9 months, p = 0.001), high stromal CD3+CD4+FOXP3+/CD3+CD4+ T cells ratio (5.5 vs. 2.5 months, p = 0.0001, in PFS), low CD3+CD4+/CD3+ T cells ratio (5.7 vs. 24.3 months, p < 0.001) and low CD3+CD45RO+/CD3+ T cells ratio (7.1 vs. 10.4 months, p = 0.033) were correlated with improved OS. Low CD3+CD4+/CD3+ T cells ratio (33.3% vs. 9.1%, p = 0.041) and high stromal CD3+CD4+Foxp3+/CD3+CD4+ T cells ratio (37.8% vs. 5.7%, p = 0.004) were significantly associated with better tumor response. GC harboring MSI-H and EBV had higher CD3+C8+/CD3+ cells ratio and CD3+CD8+ T cells density than GC with non-MSI/non EBV. Patients with MSI-H and EBV had longer OS than those with non-MSI/non-EBV (not reached to median value, 27.3 months and 7.0 months, p < 0.001).
Conclusions
Composition, density and distribution of T cell subsets in tumour were associated with the response to ICBs. mIHC is a good method to assess T cell subsets in archival tumour tissue.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Seoul National University Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5185 - Systemic administration of the hyaluronidase-expressing oncolytic adenovirus VCN-01 in patients with advanced or metastatic pancreatic cancer: first-in-human clinical trial
Presenter: Rocio Garcia-Carbonero
Session: Poster Display session 2
Resources:
Abstract
4842 - The analysis of genomic signatures of head and body/tail of pancreatic cancer in Chinese patients
Presenter: Qi Ling
Session: Poster Display session 2
Resources:
Abstract
4988 - MGMT methylation in metastatic pancreatic cancer (mPAC): a single center experience
Presenter: Monica Niger
Session: Poster Display session 2
Resources:
Abstract
5035 - Advantage of three-dimensional image analysis of pancreatic cancer using computed tomography
Presenter: Seung Bae Yoon
Session: Poster Display session 2
Resources:
Abstract
1465 - Phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) with S-1 in patients with stage IV pancreatic cancer.
Presenter: Susumu Hijioka
Session: Poster Display session 2
Resources:
Abstract
1982 - Impact of anatomic site of biliary tract tumour origin and conditional probability of survival (CS): results from 15 prospective advanced first-line clinical trial
Presenter: Mairead McNamara
Session: Poster Display session 2
Resources:
Abstract
2244 - FOLFOXIRI versus FOLFIRINOX in first-line chemotherapy in patients with advanced pancreatic cancer: a propensity score analysis
Presenter: Angélique Vienot
Session: Poster Display session 2
Resources:
Abstract
4557 - Cellfree tumor-DNA (cfDNA) as a very early predictor of therapeutic outcome in pancreatic ductal adenocarcinoma (PDAC)
Presenter: Sabine Payr
Session: Poster Display session 2
Resources:
Abstract
4406 - Comprehensive genomic profiling (CGP) of gall bladder adenocarcinoma (GBAC) in patients from distinct ancestral populations
Presenter: Milind Javle
Session: Poster Display session 2
Resources:
Abstract
4283 - Phase II Monotherapy Efficacy of Cancer Metabolism Targeting SM-88 in Heavily Pre-Treated PDAC Patients.
Presenter: Allyson Ocean
Session: Poster Display session 2
Resources:
Abstract