Decreased Anti-Tumor Cytotoxic Immunity among Microsatellite-Stable Colon Cancers from African Americans.
Colorectal cancer is a leading cause of cancer related deaths in the U.S., with African-Americans having higher incidence and mortality rates than Caucasian-Americans. Recent studies have demonstrated that anti-tumor cytotoxic T lymphocytes provide protection to patients with colon cancer while patients deficient in these responses have significantly worse prognosis. To determine if differences in cytotoxic immunity might play a role in racial disparities in colorectal cancer 258 microsatellite-stable colon tumors were examined for infiltrating immune biomarkers via immunohistochemistry. Descriptive summary statistics were calculated using two-sample Wilcoxon rank sum tests, while linear regression models with log-transformed data were used to assess differences in race and Pearson and Spearman correlations were used to correlate different biomarkers. The association between different biomarkers was also assessed using linear regression after adjusting for covariates. No significant differences were observed in CD8+ (p = 0.83), CD57+ (p = 0.55), and IL-17-expressing (p = 0.63) cell numbers within the tumor samples tested. When infiltration of granzyme B+ cells was analyzed, however, a significant difference was observed, with African Americans having lower infiltration of cells expressing this cytotoxic marker than Caucasians (p<0.01). Analysis of infiltrating granzyme B+ cells at the invasive borders of the tumor revealed an even greater difference by race (p<0.001). Taken together, the data presented suggest differences in anti-tumor immune cytotoxicity may be a contributing factor in the racial disparities observed in colorectal cancer.
Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, California, United States of America.
Ranor C B
RC
Basa
Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, California, United States of America.
Vince
V
Davies
Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, California, United States of America.
Xiaoxiao
X
Li
Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, California, United States of America.
Bhavya
B
Murali
Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, California, United States of America.
Jinel
J
Shah
Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, California, United States of America.
Bing
B
Yang
School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
Shi
S
Li
Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, California, United States of America.
Mohammad W
MW
Khan
Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, California, United States of America.
Mengxi
M
Tian
Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, California, United States of America.
Ruth
R
Tejada
Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, California, United States of America.
Avan
A
Hassan
Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, California, United States of America.
Allen
A
Washington
School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
Bhramar
B
Mukherjee
Department of Internal Medicine, Medical School, University of Michigan, Ann Arbor, Michigan, United States of America.
John M
JM
Carethers
Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, California, United States of America.
Kathleen L
KL
McGuire
D000328:Adult; D001741:Black or African American; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology; D003110:Colonic Neoplasms / Q000208:ethnology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D005260:Female; D015870:Gene Expression; D053804:Granzymes / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D044465:White People
D014408:Biomarkers, Tumor; D016827:CD8 Antigens; C508717:IL17A protein, human; D020381:Interleukin-17; D053804:Granzymes