Abstract P015: Characterization and prognostic impact of DC-HIL in advanced colorectal cancer
Authors: Khatib Jude , Chung Jin-Sung , Reddy Sarah , Chowattukunnel Nivan , Milsap Allante , Goksu Yasin , Ariizumi Kiyoshi , Kazmi Syed 
Published: January 2022

Abstract
Introduction: DC-HIL is the T cell-inhibitory receptor that is expressed by exponentially expanding CD14+HLA-DRno/low myeloid-derived suppressor cells (MDSC) and critically mediates the immunosuppressive function. We previously reported that this DC-HIL expression is associated with colorectal cancer (CRC) progression. The purpose of this investigation was to determine the correlation of DC-HIL-expressing MDSC subpopulation in blood with clinical outcomes in advanced CRC.
Methods: Patients with metastatic CRC (n = 63) were analyzed by flow cytometry for DC-HIL or PDL1 expression on blood CD14+HLA-DRno/low MDSC. A retrospective chart review was performed to obtain data on demographics, tumor, and clinical characteristics including tumor laterality, histology, mutational and microsatellite stability status, stage, metastatic sites, CEA level, and white blood cell count, and differential and treatment outcomes including response to therapy and survival. Baseline characteristics were compared using the two-tailed Student's t-test, ANOVA test, or Pearson correlation test as appropriate. Survival analysis was estimated using the Kaplan-Meier method and Cox regression model, and groups were compared using the log-rank test.
Results: Median age at diagnosis was 56 years (range 30-78) and patients were predominantly male (59%) and white (76%). Forty pts had left-sided tumors (63%), the majority had moderately differentiated adenocarcinoma (66%) and stage IV colorectal cancer at diagnosis (68%). At the time of DC-HIL collection, 95% of pts had stage IV disease. Most (95%) pts had microsatellite stable disease, 24% of pts had a KRAS mutation and 22% had a BRAF mutation, 69% of patients underwent surgical resection of the primary malignancy or metastatic site or both. Median CEA level was 40 ng/ml, median white blood cell (WBC) count was 5.9 × 109, median absolute monocyte count (AMC) was 0.64 × 109, median absolute neutrophil count (ANC) was 3.6 × 109, median monocyte to lymphocyte ratio (M/L) was 0.53 and median neutrophil to lymphocyte ratio (N/L) was 2.7. Most pts (90%) received FOLFOX chemotherapy as first-line and 84% of pts received an anti-VEGF agent throughout the course of their treatment. Median CD14+/PBMC for pts was 14.4, median %MDSC/PBMC was 7.0, median %DC-HIL+/MDSC was 66, median %DC-HIL+/MDSC/PBMC was 4.1 and median sDC-HIL was 20.0 ng/ml. Our results showed that there was a statically significant correlation between % MDSC/PBMC, %DCHIL+MDSC/PBMC, and the monocyte/lymphocyte (M/L) ratio with p=0.047 and p=0.03 respectively. There was no statistically significant correlation between DCHIL+/MDSC levels and response to therapy, time-to-next therapy (p=0.11), or overall survival (p=0.67).
Conclusion: DC-HIL+ MDSC is positively correlated with M/L ratio, a possible prognostic marker in CRC patients. DC-HIL correlates poorly with other clinical outcomes; chemotherapy response, time-to-next therapy, or overall survival.
Citation Format: Jude Khatib, Jin-Sung Chung, Sarah Reddy, Nivan Chowattukunnel, Allante Milsap, Yasin Goksu, Kiyoshi Ariizumi, Syed Kazmi. Characterization and prognostic impact of DC-HIL in advanced colorectal cancer [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P015.