Tumor-Infiltrating Lymphocytes and Colorectal Cancer Survival in African American and Caucasian Patients

Abstract

Compared with Caucasian Americans (CAs), African Americans (AAs) with colorectal cancer have poorer survival, especially younger-age patients. A robust lymphocytic reaction within colorectal cancers is strongly associated with better survival, but whether immune response impacts the disparity in colorectal cancer survival is unknown. The study population was comprised of 211 histologically confirmed colorectal cancers at the Medical University of South Carolina (Charleston, SC; 159 CAs and 52 AAs) diagnosed between Jan 01, 2000, and June 30, 2013. We constructed a lymphocyte score based on blinded pathologic assessment of the four different types of lymphocytic reactions. Cox proportional hazards regression was used to evaluate the association between the lymphocyte score and risk of death by race. Colorectal cancers in AAs (vs. CAs) had a stronger lymphocytic reaction at diagnosis. A high lymphocyte score (vs. the lowest) was associated with better survival in AAs [HR 0.19; 95% confidence interval (CI), 0.04-0.99] and CAs (HR 0.47; 95% CI, 0.15-1.45). AAs with no lymphocytic reaction (vs. other categories) had poor survival HR 4.48 (1.58-12.7) whereas no difference was observed in CAs. The risk of death in AAs (vs. CA) was more pronounced in younger patients (HR 2.92; 95% CI, 1.18-7.22) compared with older (HR 1.20; 95% CI, 0.54-2.67), especially those with lymphocytic poor colorectal cancers. The lymphocytic reaction in tumor impacted the racial disparity in survival. Our results confirm the importance of the lymphocytic score on survival and highlight the need to fully characterize the immune environment of colorectal cancers by race. .

High‐risk Stage III colon cancer patients identified by a novel five‐gene mutational signature are characterized by upregulation of IL‐23A and gut bacterial translocation of the tumor microenvironment

“…31 SMAD4 loss alters bone morphogenic protein signaling to promote CRC cell metastasis. 38,39 Our results revealed that mutations of COL6A3, LRP1B, MUC16 and FLG genes may lead to loss of barrier function or tight junction, translocation of gut bacteria and deregulation of extracellular related and immune response genes. 32 LRP1B is a member of the LDL receptor family, is involved in focal adhesion, and inhibits cell proliferation and migration.…”

“…24,36,37 TME modulatory alterations may shape immune cell infiltration into tumor tissue and the infiltration status has been confirmed to be associated with recurrence and cancerrelated death. 38,39 Our results revealed that mutations of COL6A3, LRP1B, MUC16 and FLG genes may lead to loss of barrier function or tight junction, translocation of gut bacteria and deregulation of extracellular related and immune response genes.…”

The local inflammatory response in colorectal cancer – Type, location or density? A systematic review and meta-analysis

“…Four studies had overlapping cohorts [21][22][23][24], leaving twenty-eight independent studies with a total of 11423 patients [9,. Two studies did not find a significant survival difference for any H&E-based method [9,37], whereas the other twenty-six studies found significantly prolonged survival for patients with higher local inflammatory infiltrate with a total number of 10887 patients [25][26][27][28][29][30][31][32][33][34][35][36][38][39][40][41][42][43][44][45][46][47][48][49][50][51].…”

Wd*-test: Robust Distance-Based Multivariate Analysis of Variance

“…Microbial signature approaches have been used for development of diagnostic biomarkers [8,15,16,17] or assessing di↵erences in immune gene expression [12] -highlighting the increasing importance of statistical methods to analyze clusters of microbes-genes while also taking into account patient level variables. The role of the gut microbiome in CRC disparities is likewise poorly understood [18]. Here we use a pilot CRC dataset to demonstrate the utility of W ⇤ d in uncovering signals potentially missed due to heteroscedasticity.…”