Immunotherapy in Breast Cancer

Abstract

The importance of the tumor microenvironment including immune cell infiltrates in breast cancer has long been recognized. Tumor-infiltrating lymphocytes are prognostic and predictive; however, their prevalence as well as their prognostic and predictive power are subtype-dependent and appear most prominent in aggressive subtypes like triple-negative and HER2-positive disease. The immune responses observed in many cancers are attracted by tumor-associated antigens and, as suggested by recent research, by neoantigens - immunogenic antigens encoded for by non-synonymous mutations. The appealing promise of cancer vaccines has been pursued in breast cancer for over 2 decades; however, despite much effort having been put into vaccine trials, their clinical benefit, with the exception of some encouraging preliminary results, remains disappointing. The main hurdles compromising the efficacy of these vaccination strategies are the difficulties to generate broad and robust immune responses as well as to overcome immune escape mechanisms. The remarkable efficacy of immune checkpoint inhibitors in melanoma and lung cancer has set the ground for a race in the clinical development of numerous agents targeting these immune escape mechanisms in many tumor entities. Early clinical data in metastatic breast cancer suggests at least some clinical activity. This review discusses the current status and future perspectives of immunotherapy in breast cancer.

Composite analysis of immunological and metabolic markers defines novel subtypes of triple negative breast cancer

“…The cancer microenvironment was postulated to modulate immune cell infiltration and immune cell function( 36 , 51 , 52 ). Interestingly, triple negative breast cancer tumors analyzed in this study showed strong correlation between distinct immunosuppressive features.…”

The presence of PD-1 positive tumor infiltrating lymphocytes in triple negative breast cancers is associated with a favorable outcome of disease

“…Due to its higher genetic instability, an enhanced mutational load, and the appearance of neoantigens PD-L1 expression is more frequently found in HER2-positive and triple negative BCs than in other BC sub-entities (e.g., the luminal cohorts) [ 7 ]. Moreover, PD-L1 expression has been associated with the degree of tumor infiltrating lymphocytes (TILs) [ 8 – 10 ].…”

Virus-like particle display of HER2 induces potent anti-cancer responses

“… 36 However, the inability to overcome immune-tolerogenic mechanisms has severely inhibited the development of self-antigen based vaccines, and despite much effort having been put into vaccine trials, their therapeutic efficacy remains disappointing. 41 , 42 Also taking into account data from clinical trials on other self-antigen based vaccines, it can be concluded that neither the use of potent adjuvants nor the introduction of T helper cell epitopes into the self-antigen are sufficient means to enable autoantibody responses with clinical efficacy. 30 Multivalent display ( e.g.…”