CD4+ T cells play a role in mammary carcinogenesis

It is becoming more apparent that mammary carcinogenesis may be promoted by the immune system resulting in worse prognosis in late-stage disease patients¹. The role of CD4+ T cells in promoting invasion and metastasis of mammary adenocarcinomas by regulating tumor-associated macrophages (TAMs) has recently been established.¹ CD4+ T_H0 cells are known to differentiate into multiple subtypes, T helper 1 (T_H1), T helper 2 (T_H2), T helper 17 (T_H17), T regulatory (Treg), and T follicular helper (Tfh). T_H2 cells are preferentially expressed in the MMTV-PyMT model of mammary carcinogenesis and have been shown to regulate a specific type of macrophage known as the alternatively activated (M2) macrophage. T_H2 cells have been shown to produce IL-4 attracting M2 macrophages, whereas T_H1 cells are known to be antitumorigenic, secreting IFNγ.¹ M2 macrophages present in a solid tumor, also known as M2 TAMs, are capable of providing an active invasive and metastatic environment during mammary carcinogenesis by expressing epidermal growth factor (EGF). The activation and selection of T_H2 cells during mammary carcinogenesis however, remains unknown.

T_H2 cells have the ability to activate M2 TAMs during mammary carcinogensis and suppress the activation of T_H1 cells, resulting in progression and an increase in metastatic potential.¹ Understanding the preferential activation of T_H2 cells during mammary carcinogenesis may help develop an anticancer therapeutic that would better target the specific activation of the cell population that is promoting a protumor environment, lessening the chances of metastasis and increasing the survival of patients with breast cancer.

1. DeNardo DG, Barreto BJ, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, and Coussens LM. CD4+ T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 2009: 16:91-102.