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

Abstract

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.

Twelve-year survival and immune correlates in dendritic cell–vaccinated melanoma patients

“…86-91), but by enhancing the infiltration of CD8 + T cells via secretion of chemoattractants and normalizing tumor vessels, thus providing a mechanistic link to understanding why an increased eosinophil count may herald a better outcome (92). Of note is that tumor eosinophil infiltration has been described as favorable (e.g., in colon cancer) (93) or unfavorable (94). Its occurrence and relevance in human melanoma remain to be studied in more detail, but it is striking that Soiffer et al observed both blood eosinophilia and degranulating eosinophils in regressing melanoma metastases upon vaccination with GM-CSF-secreting autologous melanoma cells (95).…”

New Insights Into the Role of Tissue Eosinophils in the Progression of Colorectal Cancer: A Literature Review

“…After scanning the titles and abstracts of the retrieved studies, we selected the full text of 15 original research articles in accordance with the objectives established and all articles were included in our review. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Data from the included studies were independently extracted from each study and comprised: author; year of publication; sample size; participants' characteristics (mean age and gender proportion); follow-up assessment; tumour classification, stage and clinicopathological features; TATE characterization (i.e. staining, count and location); and major findings.…”

“…[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Twelve studies associated TATE with survival and/or metastatic behaviour of CRC 9,11,12,[14][15][16][18][19][20][21][22][23] and three studies associated TATE with malignant progression of colorectal lesions. 10,13,17 The first set of studies evaluated 2523 CRCs.…”

“…10,13,17 The first set of studies evaluated 2523 CRCs. 9,11,12,[14][15][16][18][19][20][21][22][23] The mean age of the participants was recorded in seven studies and ranged between 62.1 and 73 years. 9,11,14,16,[21][22][23] Nine studies detailed gender proportion, totalling 835 males and 1136 females.…”

Eosinophils and Cancer – Mini Review

“…Another study published in the journal Modern Pathology in 2016. Prizement et al [3] looked at how eosinophils might predict outcomes for patients with colorectal cancer. Taghizadeh et al [4] found no associations between objective allergy markers and cancer in a total population but reported positivity and a high number of eosinophils with association to reduced risk to die of cancer in specific subgroups.…”