Role of myeloid derived hematopoietic cells in inflammation and immune tolerance to cancer

Abstract

Cancer is an organ with tumor cells and tumor microenvironment such as the immune system, stromal fibroblasts, macrophages, smooth muscle cells, endothelial cells all embedded in an extracellular matrix that fibroblasts produce. [1] [2]

Myeloid derived cells in and around tumor help cancer cells survive, grow and spread to new locations where they seed metastasis. [3]

Cancer cells from growing tumors hijack mechanisms used by the normal tissues for wound repair such as the productions of growth and angiogenic factors, matrix metalloproteinases, fibroblasts, cells of myeloid lineage and chemokines to promote their survival and growth. [4-8]

Cells of myeloid lineage origin have a crucial role in malignant organ development by protecting the growing tumor mass from immune recognition [9] hampering the immune rejection of cancer cells. [10]

Malignant tumors recruit cells of myeloid derivation to promote the growing tumor and its invasive abilities. [11] Survival of patients with adenocarcinoma of the breast, colon, lung and prostate is inversely proportional to the number of infiltrating cells of myeloid derivation of tumors. [12-15] Such malignancies are associated with shorter survival and detecting molecular signatures typical for macrophage infiltration such as CD68 in tumors herald poor diverse malignancies. [16,17]. There is two way editing of the growing malignancy and immune system of the affected patient: the malignant process shapes the immune system of the patient and at the same time the immune system of the patient shapes the growing tumor by selecting for the cancer cells resistant to immunodetection to survive and multiply. [18]