# Heterogeneous expression of ARID1A in colorectal cancer indicates distinguish immune landscape and efficacy of immunotherapy

## TL;DR

This study shows that different patterns of ARID1A expression in colorectal cancer affect immune cell infiltration and response to immunotherapy.

## Contribution

The study reveals how ARID1A expression heterogeneity influences immune landscapes and immunotherapy outcomes in CRC patients.

## Key findings

- ARID1A-deficient tumors show increased infiltration of CD8+, CD163+, and FOXP3+ immune cells.
- Only complete or partial ARID1A deficiency correlates with higher lymphocyte infiltration.
- CRC patients with clonal ARID1A deficiency do not benefit from immune checkpoint inhibitors.

## Abstract

AT-rich interaction domain 1A (ARID1A) mutant tumors show active anti-tumor immune response, which is the potential indication of immunotherapy. However, the relationship between the heterogeneous ARID1A expression and the immune response and immunotherapy efficacy in colorectal cancer (CRC) is still unclear.

We collected 1113 cases of patients with stage I-IV CRC who underwent primary resection at Harbin Medical University Cancer Hospital. ARID1A expression in CRC tissues was assessed via immunohistochemistry (IHC). CD8, CD163 and FOXP3 were stained by IHC to identify the immune landscape. Clinicopathological features of patients were compared using statistical tests like the Wilcoxon-Mann–Whitney test or χ2 tests. Kaplan–Meier survival analysis with log-rank tests were employed.

Heterogeneous ARID1A expression was categorized into integrity expression, complete expression deficiency (cd-ARID1A), partial expression deficiency (pd-ARID1A), and clonal expression deficiency (cld-ARID1A). ARID1A-deficient expression was significant association with dMMR (P value < 0.001). Patients with ARID1A deficiency, compared to ARID1A-proficient patients, exhibited increased infiltration levels of CD8 + P value < 0.0001), CD163 + P value < 0.001), and FOXP3 + P value < 0.001).cells within the tumor tissue. However, in different subgroups, only samples with complete or partial deficiency of ARID1A showed a higher abundance of lymphocyte infiltration. In patients with ARID1A-clonal expression deficiency tumor, the infiltration patterns of three immune cell types were comparable to those in ARID1A-proficient patients. Heterogeneous ARID1A expression is related to the different prognosis and immunotherapythe efficacy in CRC patients.

Heterogeneous ARID1A expression is accompanied by a different immune landscape. CRC patients with ARID1A-clonal expression deficiency do not benefit from the treatment of immune checkpoint inhibitors (ICIs).