Tumor eosinophil infiltration and improved survival of colorectal cancer patients: Iowa Women’s Health Study

The role of the innate immune response in colorectal cancer is understudied. We examined the survival of colorectal cancer patients in relation to eosinophils, innate immune cells, infiltrating the tumor. Tissue microarrays were constructed from paraffin-embedded tumor tissues collected between 1986–2002 from 441 post-menopausal women diagnosed with colorectal cancer in the Iowa Women’s Health Study. Tissue microarrays were stained with an eosinophil peroxidase antibody. Eosinophils in epithelial and stromal tissues within the tumor (called epithelial and stromal eosinophils, hereafter) were counted and scored into 3 and 4 categories, respectively. In addition, the degree of eosinophil degranulation (across epithelial and stromal tissues combined) was quantified and similarly categorized. We used Cox regression to estimate the hazard ratios and 95% confidence interval for all-cause and colorectal cancer death during five-year follow-up after diagnosis and during follow-up through 2011 (“total follow-up”). The hazard ratios associated with eosinophil scores were adjusted for age of diagnosis, SEER stage, tumor grade, body mass, and smoking history. High tumor stromal eosinophil score was inversely correlated with age and stage, and was associated with a decreased risk for all-cause and colorectal cancer death: hazard ratios (95% confidence intervals) were 0.61 (0.36–1.02; P-trend =0.02) and 0.48 (0.24–0.93; P-trend =0.01), respectively, during the five-year follow-up for the highest versus lowest category. The inverse associations also existed for total follow-up for all-cause and colorectal cancer death for the highest versus lowest stromal eosinophil score: hazard ratios (95% confidence intervals) were 0.72 (0.48–1.08; P-trend =0.04) and 0.61 (0.34–1.12; P-trend =0.04), respectively. Further adjustment for treatment, comorbidities, additional lifestyle factors, tumor location or molecular markers did not markedly change the associations, while adjustment for cytotoxic T-cells slightly attenuated all associations. The infiltration of tumors with eosinophils, especially in stromal tissue, may be an important prognostic factor in colorectal cancer.