# Clinical and Immunologic Characteristics of Colorectal Cancer Tumors Expressing LY6G6D

## TL;DR

This study explores the clinical and immune features of colorectal cancer tumors with high LY6G6D protein expression to guide future therapies.

## Contribution

The study identifies LY6G6D as a CRC-specific target associated with specific genomic and immune profiles.

## Key findings

- LY6G6D is expressed in microsatellite stable colorectal cancer tumors and is linked to left-side tumors and canonical genomic subgroups.
- Tumors with APC and p53 mutations show elevated LY6G6D levels and lack immune cell infiltration.
- LY6G6D is associated with an inert immune microenvironment, suggesting potential for T cell engager therapies.

## Abstract

The identification of targets that are expressed on the cell membrane is a main goal in cancer research. The Lymphocyte Antigen 6 Family Member G6D (LY6G6D) gene codes for a protein that is mainly present on the surface of colorectal cancer (CRC) cells. Therapeutic strategies against this protein like the development of T cell engagers (TCE) are currently in the early clinical stage. In the present work, we interrogated public genomic datasets including TCGA to evaluate the genomic and immunologic cell profile present in tumors with high expression of LY6G6D. We used data from TCGA, among others, and the Tumor Immune Estimation Resource (TIMER2.0) platform for immune cell estimations and Spearman correlation tests. LY6G6D expression was exclusively present in CRC, particularly in the microsatellite stable (MSS) subtype, and was associated with left-side tumors and the canonical genomic subgroup. Tumors with mutations of APC and p53 expressed elevated levels of LY6G6D. This protein was expressed in tumors with an inert immune microenvironment with an absence of immune cells and co-inhibitory molecules. In conclusion, we described clinical, genomic and immune-pathologic characteristics that can be used to optimize the clinical development of agents against this target. Future studies should be performed to confirm these findings and potentially explore the suggested clinical development options.