The aim of the study was to determine the human leucocyte antigen class-I (HLA-I), programmed death-ligand 1 (PD-L1) expression and tumour-infiltrating lymphocytes (TILs) of microsatellite instability-high gastric cancer.
The HLA-I expression type was determined by immunohistochemistry of HLA-A, HLA-B, HLA-C and β2-microglobulin in the centre of the tumour (CT) and in the invasive margin (IM) of samples from 293 patients (total loss vs. preserved type). PD-L1 expression and TIL density was examined immunohistochemically. HLA-I genotyping was also performed.
The expression loss of the HLA-I molecules was significantly associated with low TIL density. According to survival analyses, the HLA-I expression type and PD-L1 positivity were not independent prognostic factors. The TIL density had no prognostic implication when survival analysis was performed for the whole patient group; however, high CD8+ TIL infiltration was significantly associated with good prognosis in only HLA-I-preserved-type/PD-L1-positive group (p = 0.034). The homozygosity of the HLA-I allele was more frequently observed in the total loss type group.
We confirmed differential prognostic implication of CD8+ TILs according to the HLA-I and PD-L1 expression. Determination of the HLA-I expression could be helpful to select patients who would benefit from anti-PD-1/PD-L1 therapy.
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Ethics approval and consent to participate
The study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (reference: B-1702/383-301) and was carried out in accordance with the recommendations of the Declaration of Helsinki for biomedical research involving human subjects. The Institutional Review Board waived the need for written informed consent under the condition of anonymisation and no additional intervention to the participants.
Consent to publish
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
The authors declare no competing interests.
This research was supported by a Basic Science Research Programme through the National Research Foundation (NRF) funded by the Ministry of Education, Republic of Korea (NRF-2016R1D1A1B03931744).
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Kwak, Y., Koh, J., Park, Y. et al. Differential prognostic impact of CD8+ T cells based on human leucocyte antigen I and PD-L1 expression in microsatellite-unstable gastric cancer. Br J Cancer 122, 1399–1408 (2020). https://doi.org/10.1038/s41416-020-0793-y