Abstract
ABSTRACTObesity is a well-established risk factor for colorectal cancer (CRC), but the association with the tumor microenvironment has been sparsely described. Herein, we examined the relationship between pre-diagnostic anthropometry and CRC risk according to tumor immune cell composition, with particular reference to potential sex differences.The density of different immune cell subsets was assessed by immunohistochemistry in tissue microarrays with tumors from 584 incident CRC cases in a prospective, population-based cohort (n = 28098). Multivariable Cox regression models, adjusted for age, smoking, alcohol intake, and educational level, were applied to calculate risk of immune marker-defined CRC in relation to quartiles of pre-diagnostic height, weight, body mass index (BMI), waist and hip circumferences, waist-hip ratio (WHR), and body fat percentage (BFP).Obesity was all over significantly associated with risk of CRC with low density of FoxP3+ T cells and low programmed cell-death protein 1 (PD-L1) expression on tumor cells, but with high density of CD8+ T cells and CD20+ B cells. In women, obesity was significantly associated with risk of PD-L1 high tumors (p= 0.009 for weight, p= 0.039 for BMI). Contrastingly, in men, obesity defined by all anthropometric factors was significantly associated with PD-L1 low tumors (p= 0.005 for weight, p = 0.002 for BMI, p<0.001 for waist, p= 0.011 for hip, p<0.001 for WHR, and p= 0.004 for BFP).In summary, obesity appears to influence the immune landscape of CRC, possibly in a sex-dependent manner. Thus, anthropometry and sex may be important factors to take into account when assessing the prognostic or predictive value of relevant complementary immune biomarkers.
Highlights
A plethora of studies have examined the relationship between body weight and risk of colorectal cancer (CRC), mainly demonstrating a positive association between high weight or body mass index (BMI) and an increased risk of CRC.[1,2,3] this association mainly seems to apply to colon cancer,[1] and the relative risk is higher in men than in women.[4]
Prospective cohort study, we have investigated the relationship between obesity and risk of CRC subtype defined by the character of the tumor immune microenvironment, with particular reference to potential difference between sexes
As the hitherto first study to investigate the impact of obesity on the expression of programmed cell-death ligand 1 (PD-L1) in CRC, the results demonstrated that several anthropometric factors were associated with risk tumors with of low immune cell-specific
Summary
A plethora of studies have examined the relationship between body weight and risk of colorectal cancer (CRC), mainly demonstrating a positive association between high weight or body mass index (BMI) and an increased risk of CRC.[1,2,3] this association mainly seems to apply to colon cancer,[1] and the relative risk is higher in men than in women.[4]. The associations between the density of different immune cell subsets and disease stage, grade, tumor location, and mutation status have been investigated in numerous studies,[6,8] in the investigated cohort.[9,10,11] the relationship with obesity has been sparsely described
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