Immunological hallmarks of stromal cells in the tumour microenvironment

Abstract

A dynamic and mutualistic interaction between tumour cells and the surrounding stroma promotes the initiation, progression, metastasis and chemoresistance of solid tumours. Far less understood is the relationship between the stroma and tumour-infiltrating leukocytes; however, emerging evidence suggests that the stromal compartment can shape antitumour immunity and responsiveness to immunotherapy. Thus, there is growing interest in elucidating the immunomodulatory roles of the stroma that evolve within the tumour microenvironment. In this Review, we discuss the evidence that stromal determinants interact with leukocytes and influence antitumour immunity, with emphasis on the immunological attributes of stromal cells that may foster their protumorigenic function.

Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue

“…Three major terminally differentiated cell types are present in the colon: colonocytes or absorptive cells, mucus-secreting goblet cells, and peptide hormone-secreting endocrine cells. The lamina propria consists of a more heterogeneous collection of cell types, including fibroblasts, lymphocytes, macrophages, eosinophilic leukocytes, and mast cells (55). A punch biopsy also accesses part of the submucosa directly below the crypts, further contributing to the heterogeneity of the stromal fraction.…”

“…These data provide insight into the gene expression landscape of the normal epithelium and stroma prior to the onset of intestinal tumorigenesis. This is noteworthy because the development of cancer is intimately linked to cross talk between cancer cells and the surrounding stromal cells (microenvironment) (19,43,55).…”

“…The development of colon cancer is intimately regulated by cross talk between the complex milieu of the stroma, containing fibroblasts, inflammatory immune cells and vascular cells, and the intestinal stem cell niche (19,28,43,55). Thus, colonic biopsies represent intestinal-specific transcriptional patterns consisting of signals originating from stromal and epithelial cells (7,12,24).…”

The Future of Checkpoint Blockade to Treat Cancer Patients

“…Several researchers had been showed that distinct microenvironments where tumor-associated macrophages (TAM) promote cancer cell motility, angiogenesis and metastasis. In addition, there is strong evidence that regulatory T cell populations (Treg) can migrate into tumors and suppress adequate anti-tumor responses in the tumor microenvironment, thus contributing to the prosperity and growth of human tumors [24].…”

“…Several researchers had been showed that distinct microenvironments where tumor-associated macrophages (TAM) promote cancer cell motility, angiogenesis and metastasis. In addition, there is strong evidence that regulatory T cell populations (Treg) can migrate into tumors and suppress adequate anti-tumor responses in the tumor microenvironment, thus contributing to the prosperity and growth of human tumors [24].Reasons for limited immune response against tumor cells include immune regulation mediated by cancer cells and immune cells profile on microenvironment. Indeed, cancer cells are able to shape the innate immune response to obtain growth factors, pro-angiogenic factors, and other elements that stimulate tumor growth, development, invasion, and metastasis.…”