Abstract
Worldwide, breast cancer is the most important type of cancer in women with regard to incidence and prevalence. Several risk factors interact to increase the probability of breast cancer development. Biological environmental contaminants such as infectious agents play a significant role in tumor development, and helminths have been recognized as cancer enhancers or inducers due to their ability to regulate the host immune response. Toxocara canis is a zoonotic and cosmopolite nematode with immuno-regulatory abilities. T. canis infection has been related to T helper type-2 cell (Th2 or type 2) and regulatory responses. Type 2 and regulatory immune responses may favor the development of comorbidities that are usually controlled or eliminated through a type 1 response such as cancer. The aim of this study was to determine whether T. canis infection alters mammary tumor growth through modulation of the immune response. Infected mice developed larger tumors. Tumor immune cell milieu analysis revealed that infection reduced the proportions of CD8+ lymphocytes and increased the proportions of F4/80+ macrophages and CD19+ B cells. These changes were accompanied by a type 2 local response represented by increased amounts of IL-4 and VEGF and a regulatory microenvironment associated with higher IL-10 levels. Thus, this study demonstrates that T. canis infection enhances tumor development and suggests that this is through modulation of the tumor immune microenvironment.
Highlights
Breast cancer is the most prevalent cancer in women and their leading cause of cancer death [1]
Because T. canis infection modifies the mouse’s immune systemic response toward type 2 and regulatory responses [28], we wondered whether this change may reach the tumor microenvironment
Cancer research has been focused on a cellcentral approach based on cancer cell signaling pathways and DNA changes [32], with the main goal of finding a cancer cure. This type of research has made some advances in cancer cell biology and treatment, but it has neglected some cancer risk factors related to the interactions among cells, the tumor microenvironment, and infectious agents
Summary
Breast cancer is the most prevalent cancer in women and their leading cause of cancer death [1]. First and foremost is gender; women present with breast cancer more frequently than men [1]. Risk factors such as alcohol intake, smoking, and hormone replacement treatment, among others, have been linked to breast cancer development [2]. 15% of different cancer types are linked to viral, bacterial, or parasite infections [4]. In this sense, some helminthic infections play an important role in cancer progression. The helminths are ubiquitous parasites that cause chronic infections in human, livestock, and domestic animals; they include platyhelminths (flatworms) and nematodes (roundworms) [5, 6]. Nematode infections are reported as colon cancer enhancers (Heligmosomoides polygyrus) [9]
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