How immune cells can promote cancer progression

Did you know that the immune system can actually help promote cancer?

The tumor microenviroment is a complex milieu containing stromal cells (such as immune cells and fibroblasts), signaling molecules such as cytokines, and extracellular matrix. There is growing evidence that immune cells in the tumor microenvironment can be tricked by tumor cells to help the cancer grow by promoting angiogenesis (new blood vessel formation), suppressing the anti-tumor immune response, and promoting growth by secretion of growth factors. Immune cells are also thought to aid in the metastatic process as well as confer resistance to various chemotherapies.  It is therefore extremely important to further understand the interplay between cancer cells and cells in the tumor microenvironment.

Immune cells present in the tumor microenviroment include effectors of adaptive immunity (immunity guided by specific identification of pathogens) such as T-cells, dendritic cells, and to a lesser extent, B-cells. Also present are cells of the innate immune system (non-specific identification of pathogens) such as macrophages and other myeloid derived cells, leukocytes, and rarely natural killer cells.

Cytotoxic T-cells, can kill tumor cells by secreting cytotoxic substances such as perforin, granzymes, and granulysin.  Their activity can be regulated by various cytokines or signals from helper T-cells or other cells in the tumor microenviroment.

The myeloid lineage in tumors, generally termed myeloid suppressor cells (MSC), are considered key in the aberrant growth promotion of tumor cells and suppression of the anti-tumor immune response.  They are considered the major inflammatory cells of many solid tumors, including breast and prostate. MSCs in tumors include, tumor associated macrophages (TAM), polymorphonuclear and monocytic myeloid derived suppressor cells (PMN and MO-MDSC)Similar to T-cells, MSC activity can also be modulated by signaling factors from the microenvironment and can be induced to become more anti-tumor and pro-inflammatory.

MSCs share similar functions and their role in cancer promotion is said to be several fold.  First, they can suppress the adaptive immune response and thus function as regulators of anti-tumor T-cell activity. Second, they can induce angiogenesis through secretion of vascular endothelial growth factors (VEGFs) and matrix remodeling enzymes.  Additionally, they can also promote growth and proliferation by secreting growth factors such as epidermal growth factor (EGF), fibroblast growth factors (FGFs) among others.

In non-pathological conditions, myeloid derived cells play a large role in wound repair also by promoting angiogenesis, growth and proliferation. Therefore, it is easy to deduce that during chemotherapy or any type of anti-tumor treatment a dying tumor cell may appear as a wound that needs repair or healing.

Further research to better understand the interplay of tumor cells and the microenvironment as well as how to better fine-tune the tumor microenvironment against cancer is imperative for the development of better therapeutic agents.