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
3248 - Second-line palliative systemic treatment for synchronous metastatic esophagogastric cancer: a population-based study
Presenter: Willemieke Dijksterhuis
Session: Poster Display session 2
Resources:
Abstract
4331 - STING Agonist, ADU-S100, Yields Potent Antitumor Activity and Therapeutically Favorable Immune Profile in an Esophageal Adenocarcinoma Model
Presenter: Ali Zaidi
Session: Poster Display session 2
Resources:
Abstract
1770 - Increased assessment of HER2 in metastatic gastroesophageal cancer patients: a nationwide population-based cohort study
Presenter: Willemieke Dijksterhuis
Session: Poster Display session 2
Resources:
Abstract
3755 - A new docetaxel (DOC)-based triplet regimen does not improve the outcome of metastatic (M) or locally advanced (LA) gastric cancer (GC) as compared with an epirubicin (EPI) standard triplet regimen: a GISCAD trial.
Presenter: Roberto Labianca
Session: Poster Display session 2
Resources:
Abstract
2211 - First-line pembrolizumab (P), trastuzumab (T), capecitabine (C) and oxaliplatin (O) in HER2-positive metastatic esophagogastric adenocarcinoma.
Presenter: Yelena Janjigian
Session: Poster Display session 2
Resources:
Abstract
3046 - Monitoring patient-specific mutation in ctDNA and CTC for tumor response evaluation after neoadjuvant chemotherapy in locally advanced gastric cancer (NCT03425058)
Presenter: Tao Fu
Session: Poster Display session 2
Resources:
Abstract
4628 - Gastric cancer screening in BRCA 2 gene mutation carriers: should it be recommended?
Presenter: Inês Oliveira
Session: Poster Display session 2
Resources:
Abstract
2127 - Interim analysis of an observational/translational study for nivolumab treatment in advanced gastric cancer: JACCRO GC-08 (DELIVER trial)
Presenter: Yu Sunakawa
Session: Poster Display session 2
Resources:
Abstract
2264 - Prediction of S-1 adjuvant chemotherapy efficacy in Stage II/III gastric cancer treatment based on comprehensive gene expression analysis
Presenter: Masanori Terashima
Session: Poster Display session 2
Resources:
Abstract
2444 - Assessing the clinical utility of circulating tumour DNA through longitudinal liquid biopsy sampling in Oesophageal adenocarcinoma
Presenter: Emma Ococks
Session: Poster Display session 2
Resources:
Abstract