# Chemical complementarity of tumor resident, T-cell receptor CDR3s and renalase-1 correlates with increased melanoma survival

## TL;DR

Higher chemical compatibility between T-cell receptors and the renalase-1 protein is linked to better survival in melanoma patients.

## Contribution

The study identifies a novel correlation between TCR CDR3-renalase-1 chemical complementarity and melanoma survival.

## Key findings

- Increased TCR CDR3-renalase-1 complementarity scores correlate with improved overall survival in melanoma patients.
- High complementarity is more strongly associated with survival in cases of low renalase-1 gene expression.
- The RP220 epitope of renalase-1 is a key interaction site linked to melanoma growth inhibition.

## Abstract

Overexpression of the secretory protein renalase-1 negatively impacts the survival of melanoma and pancreatic cancer patients, while inhibition of renalase-1 signaling drives tumor rejection by promoting T-cell activation. Thus, we investigated the chemical complementarity between melanoma-resident, T-cell receptor (TCR) complementarity-determining region 3 (CDR3) amino acid sequences (AAs) and the renalase-1 protein. Increasing complementarity of TCR CDR3s to renalase-1 AAs, as assessed by a chemical complementarity scoring algorithm, was associated with improved overall survival (OS) in melanoma patients. The expression levels of several immune signature genes were significantly, positively correlated with increasing TCR CDR3-renalase-1 complementarity scores. Additionally, the survival association observed with high complementarity of TCR CDR3s to renalase-1 AAs was more robust in cases with low renalase-1 gene expression levels. Mapping of TCR CDR3-renalase-1 in silico interaction sites identified major epitope candidates including RP220, the signaling module of the renalase-1 protein, consistent with the fact that a monoclonal antibody to RP220 is a potent inhibitor of melanoma growth. These findings indicate that renalase-1 is a potential antigen for TCR recognition in melanoma and could be considered as a target for immunotherapy.