Adaptive immune responses associated with breast cancer relapse.
The generation, survival, and differentiation of breast cancer stem cells (BCSC) in immunocompetent hosts remain elusive. Some investigators have shown that BCSC can be induced from epithelial tumor cells by the pathologic epithelial to mesenchymal transition (EMT). Emerging evidence suggests that the induction of EMT among epithelial tumor cells originates from signals produced by the non-tumor cells that constitute the tumor microenvironment, including the immune effectors that infiltrate the tumors. Thus, this suggests that the immune system not only has anti-tumor function, but also paradoxically immunoedits tumors, facilitating tumor escape and progression. Indeed, many studies in human breast cancers show both positive and negative associations between the infiltration of various immune effectors (e.g., CD4 and CD8 T cells) and the propensity to relapse with metastatic disease. These observations suggest that distinct types of immune effector cells may induce or inhibit tumor relapse. This review focuses on recent advances in identifying components of the immune system that may directly induce tumor escape and relapse. We propose that levels of interferon (IFN)-γ production or levels of the expression of IFN-γ receptor α on tumor cells may determine whether tumor inhibitory or relapse-promoting effect of IFN-γ may prevail.
Department of Microbiology and Immunology, Massey Cancer Center, Virginia Commonwealth University, 401 College Street, Box 980035, Richmond, VA 23298, USA.
Kyle K
KK
Payne
Masoud H
MH
Manjili
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D007107:Immune System; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000166:cytology; D051381:Rats; D012008:Recurrence
D007371:Interferon-gamma