Search

A cancer mass consists of a complex composition of cancer cells, stromal cells, endothelial cells and also immune cells, which can represent more than half of the cellularity of a solid cancer. These immune cells become activated when they sense cancer antigens and stress ligands. Innate immune cells also detect various aspects of cellular stress that characterize a growing tumor mass. These key hallmarks of cellular stress are also detected by the cancer cell itself. In this review, we highlight studies that show that the cancer cell itself could be considered an 'innate cell' that senses and reacts to non-immunologic hallmarks of cancer, including displaced nucleic acids, proteotoxic stress, oxidative stress, and metabolic alterations., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Cancer cells condition macrophages and other inflammatory cells in the tumor microenvironment so that these cells are more permissive for cancer growth and metastasis. Conditioning of inflammatory cells reflects, at least in part, soluble mediators (such as transforming growth factor β and IL-4) that are released by cancer cells and alter the phenotype of cells of the innate immune system. Signaling pathways in cancer cells that potentiate this activity are incompletely understood. The urokinase receptor (uPAR) is a cell-signaling receptor known to promote cancer cell survival, proliferation, metastasis, and cancer stem cell-like properties. The present findings show that uPAR expression in diverse cancer cells, including breast cancer, pancreatic cancer, and glioblastoma cells, promotes the ability of these cells to condition co-cultured bone marrow-derived macrophages so that the macrophages express significantly increased levels of arginase 1, a biomarker of the alternatively activated M2 macrophage phenotype. Expression of transforming growth factor β was substantially increased in uPAR-expressing cancer cells via a mechanism that requires uPA-initiated cell signaling. uPAR also controlled expression of IL-4 in cancer cells via a mechanism that involves activation of ERK1/2. The ability of uPAR to induce expression of factors that condition macrophages in the tumor microenvironment may constitute an important mechanism by which uPAR promotes cancer progression., (Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

When immune cells and developing tumor cells localize to a common microenvironment, an assemblage of interactions takes place; this results in either tumor destruction by way of immunosurveillance or tumor outgrowth. These events put a functional imprint onto the emerging tumor repertoire because tumor cells arising in the presence of a fully functional immune system are less immunogenic than those that develop in the absence of immunity (i.e. in RAG2(-/-) and perforin(-/-) mice). However, other studies suggest that the immune system can also actively promote formation of certain tumors. These apparent disparate effects of immunity on tumorigenesis provide a unique model for study of the decision-making process that dictates immune function within a tumor.