Association of the tissue infiltrated and peripheral blood immune cell subsets with response to radiotherapy for rectal cancer

Abstract

Background Tumor microenvironment plays pivotal roles in carcinogenesis, cancer development and metastasis. Composition of cancer immune cell subsets can be inferred by deconvolution of gene expression profile accurately. Compositions of the cell types in cancer microenvironment including cancer infiltrating immune and stromal cells have been reported to be associated with the cancer outcomes markers for cancer prognosis. However, rare studies have been reported on their association with the response to preoperative radiotherapy for rectal cancer. Methods In this paper, we deconvoluted the immune/stromal cell composition from the gene expression profiles. We compared the composition of immune/stromal cell types in the RT responsive versus nonresponsive for rectal cancer. We also compared the peripheral blood immune cell subset composition in the stable diseases versus progressive diseases of rectal cancer patients with fluorescence-activated cell sorting from our institution. Results Compared with the non-responsive group, the responsive group showed higher proportions of CD4+ T cell (0.1378 ± 0.0368 vs. 0.1071 ± 0.0373, p = 0.0215), adipocytes, T cells CD4 memory resting, and lower proportions of CD8+ T cell (0.1798 ± 0.0217 vs. 0.2104 ± 0.0415, p = 0.0239), macrophages M2, and preadipocytes in their cancer tissue. The responsive patients showed a higher ratio of CD4+/CD8+ T cell proportions (mean 0.7869 vs. 0.5564, p = 0.0210). Consistently, the peripheral blood dataset showed higher proportion of CD4+ T cells and higher ratio of CD4+/CD8+ T cells, and lower proportion of CD8+ T cells for favorable prognosis. We validated these results with a pooled dataset of GSE3493 and GSE35452, and more peripheral blood data, respectively. Finally, we imported these eight cell features including eosinophils and macrophage M1 to Support Vector Machines and could predict the pre-radiotherapy responsive versus non-responsive with an accuracy of 76%, ROC AUC 0.77, 95% confidential interval of 0.632–0.857, better than the gene signatures. Conclusions Our results showed that the proportions of tumor-infiltrating subsets and peripheral blood immune cell subsets can be important immune cell markers and treatment targets for outcomes of radiotherapy for rectal cancer.

Construction and validation of prognostic risk model based on radiosensitivity-related immune genes in rectal cancer

“…In recent years, more attention has been paid to the immune genes related to RC, and their effect on radiosensitivity and prognosis. Immune genes are associated with immune regulation and microenvironment of the tumors, the expression of which can affect patients' response to radiotherapy[8, 9,10].In this study, we established and validated a prognostic risk model based on four RRIGs (BMP2, COLEC10, MASP2, GCGR), the model can serve as an independent prognostic factor and has potential value in predicting the prognosis of RC patients.…”

Neoadjuvant chemoradiotherapy combined with sequential perioperative toripalimab in locally advanced esophageal squamous cell cancer

“…These findings were consistent with that of some previous studies. [33][34][35] Nevertheless, these preliminary results still require confirmation in a larger population. Furthermore, it is important to thoroughly analyze the consistency of the immune cell subset compositions between peripheral blood and tumor microenvironment, as well as the specific status and function of T cell subsets.…”

Immune Response and Immune Checkpoint Molecules in Patients with Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy: A Review

“…Another study by Napolitano et al suggested that an abundance of FOXP3+ regulatory T-cells after CRT was linked with the poor response of rectal tumors [153]. In contrast, Zhu et al found that high levels of CD4+ circulating T-cells were correlated with better tumor response to RT and better prognosis [154].…”