Abstract 1017: Characterizing immune cell infiltration in colorectal cancer tumor microenvironment among Native Hawaiians
Authors: Fu Yuanyuan , Quintal Gino , Nasu Masaki , Jijiwa Mayumi , Rai Sudhir K. , Mohd-Ibrahim Isam , Chen Yu , Yang Hua , Wang Zhanwei , Wai Christina , Chan Owen , Hernandez Brenda Y. , Deng Youping 
Published: March 2024

Abstract
Background Colorectal cancer (CRC) is recognized as a heterogeneous disease, ranking third in new cancer diagnoses and second in cancer-related deaths globally and nationally. CRC incidence is higher in the state of Hawaii compared to the U.S. overall. This study focuses on profiling immune cell infiltration in Native Hawaiian(NH)-specific CRC tumor microenvironments. Identifying the race-specific tumor infiltrating microenvironment may uncover potential mechanisms for CRC development in the NH population.
Methods Deidentified, archival formalin-fixed paraffin-embedded tumor samples from Native Hawaiian patients diagnosed with primary CRC between 1990 and 2006 were obtained from the Hawaii Tumor Registry. RNA was extracted from tumor and adjacent normal tissues. RNA-seq data from Caucasian American (CA) CRC samples were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Differentially expressed genes for each cohort were identified via DESeq2 with Benjamini-Hochberg multiple testing q-value&lt;0.05 and a cutoff of 2-fold change. From the gene expression profiles, we applied the ESTIMATE algorithm to calculate the overall immune cell infiltration score for each sample. Based on a deconvolution algorithm, known as CIBERSORT to estimate the abundance of 22 immune cell types, we profiled the tumor-infiltrating immune cells present in each cohort’s paired samples, respectively. To improve the accuracy, p-value and root mean squared error were counted for each sample. Data with p&lt;0.05 were filtered and selected for the next analysis. The fraction of immune cell subpopulations was evaluated and compared between paired tumor and adjacent normal tissues in NH and CA cohorts.
Results In the NH cohort, we found the overall immune cell infiltration score was significantly lower in cancer tissues than the adjacent normal tissues (p&lt;0.05), and there were significantly higher fractions of activated dendritic cells, resting natural killer (NK), and follicular helper T cells in tumor tissues compared to adjacent non-tumor tissues (p&lt;0.05). Furthermore, the fractions of activated NK cells and plasma cells were significantly lower in tumor tissues than in adjacent non-tumor tissues in NH (p&lt;0.05). Resting NK cells are upregulated in both the NH and the CA cohorts, while plasma cells are the only immune cell type downregulated in either cohort. In the NH cohort, activated dendritic cells and follicular helper T cells are exclusively upregulated, while activated NK cells are downregulated relative to the CA cohort.
Conclusion This study demonstrates that the NH cohort displays distinctive immunological variances between tumor and adjacent non-tumor tissues which distinguishes them from the CA cohort. This emphasizes the significance of acknowledging population-specific genetic variations which may help understand race specific difference in CRC.
Citation Format: Yuanyuan Fu, Gino Quintal, Masaki Nasu, Mayumi Jijiwa, Sudhir K. Rai, Isam Mohd-Ibrahim, Yu Chen, Hua Yang, Zhanwei Wang, Christina Wai, Owen Chan, Brenda Y. Hernandez, Youping Deng. Characterizing immune cell infiltration in colorectal cancer tumor microenvironment among Native Hawaiians [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1017.