2282P - Tissue glycan profiling in predicting immunotherapy response in renal cell carcinoma and hepatocelllular carcinoma

Background

The immune system can eliminate malignancy by identifying antigenic peptide epitope presented by neoplastically transformed cells. Immune cells recognize abnormal glycosylation on cancer cells, and this recognition often leads to an inhibitory immune process. We designed a biomedical study to evaluate the role of tissue glycan in predicting immunotherapy response in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC).

Methods

Thirty-two patients with intermediate/poor risk RCC and advanced HCC (eight respondents and eight non-respondents each) who had received first line immunotherapy-based therapy were identified. The overall survival for RCC and HCC non-respondent cohort was 27.9 months and 8 months respectively but was immature for the respondent cohort. Response criteria to immunotherapy was decided based on the immune related response criteria (iRECIST) where good response is defined as complete or partial response while poor respondent was defined as progression of disease with median survival shorter than reported. Next, we compare the relative abundance and spatial distribution of the glycans in the responder versus non-responder tissue sections given regional characterizations within the tissues. This helps points out the distinct glycans between the responder versus non-responder tissue sections that could serve as potential biomarkers which can then be used in future diagnostic and/or therapeutic intervention. We used the MALDI analysis by rapifleX.

Results

MALDI imaging of HCC and RCC responder versus non-responder tissue section was successfully demonstrated. There was distinct responder versus non responder glycan markers demonstrated by unsupervised segmentation analysis, showing specific layers of glycan organization in the different tissue regions. There are several glycan peaks showing distinctive expression between respondent versus non respondent patients. PCA showed distinguishable variances across each annotated structures derived from segmentation analysis.

Conclusions

Distinct glycan profile markers were observed between both responder and non-responder cohort showing specific layers of glycan organization in the different tissue regions.

Clinical trial identification

NHG DSRB Ref: 2021/01072

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

NMC CG program.

Disclosure

All authors have declared no conflicts of interest.