2439 - The analysis of T cell subsets and clinical efficacy of immune checkpoint blockades in patients with advanced gastric cancer using multiplex immunohistochemistry

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.