Clinicopathological correlation of immune response in human cancers

Background: The clinicopathologic association of tumor immune response is largely unknown. We systematically investigated this matter in human cancers. Results: Different cancer types exhibited distinct immune gene profiling. Four cancer types exhibited a significant and positive correlation of immune response with patient age. Significant but inconsistent correlation of immune response was observed with gender, surgical stage, and TNM stage in a small number of cancer types. In contrast, the histological grade appears to have much stronger and more consistent association with immune response as compared to the other clinicopathologic factors. Specifically, patients with high grade had significantly higher immune responses than those with low grade in 5 out of 12 analyzed cancer types. In addition, both histological and molecular classifications had a significant and strong association with tumor immune response. Methods: t-distributed stochastic neighbor embedding was used to assess similarity of immune gene profiling in human cancers. The Mann-Whitney or Kruskal-Wallis test was, respectively, used to compare the tumor immune response in two or more groups that were stratified by patient clinicopathological characteristics, such as gender, grade, stage (including surgical and TNM stage), histology, and molecular subtypes. Spearman correlation with student's t-test was used to examine the association of patient age with immune response. Multiple tests with the Benjamini-Hochberg correction also were performed. Conclusions: Tumor grade should be taken into account in selection of patient candidates for immunotherapy. Prospective verification is needed before use of the findings for clinical practice.