Cellular and Molecular Biology

Differential prognostic impact of CD8+ T cells based on human leucocyte antigen I and PD-L1 expression in microsatellite-unstable gastric cancer

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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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Fig. 1: Immunohistochemistry results of a representative case.
Fig. 2: Assessment of HLA-I expression type.
Fig. 3: Differentiated tumour-infiltrating lymphocytes (TILs) densities according to HLA-I expression type and PD-L1 CPS status.
Fig. 4: Differential prognostic implication of CD8+ TIL according to HLA-I expression type and PD-L1 CPS status.
Fig. 5: HLA-I genotyping results for 34 patients using matched blood sample.

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Affiliations

Authors

Contributions

Y.K. analysed overall data and wrote this paper. J.K. helped reading of IHC and the data analysis. Y.P. helped reading of IHC and the data analysis. Y.J.H. performed the HLA genotyping analysis and helped the data analysis. K.U.P. helped the HLA genotyping analysis and contributed data collection. H.-H.K. helped the collection of clinical data. D.J.P. collected the clinical data. S.-H.A. helped the collection of clinical data. W.H.K. contributed the experiment and data analysis. H.S.L. collected all clinicopathologic data and designed this study.

Corresponding author

Correspondence to Hye Seung Lee.

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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.

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Not applicable.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare no competing interests.

Funding information

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

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