Protective effect of naturally occurring anti-HER2 autoantibodies on breast cancer

Abstract

Anti-HER2-autoantibodies (HER2-AAbs) are found in breast cancer patients as well as healthy individuals. However, the clinical relevance of the antibodies is unknown. We established an enzyme-linked immunosorbent assay with high sensitivity and quantified serum HER2-AAbs in 100 healthy women, 100 untreated patients with ductal carcinoma in situ (DCIS), and 500 untreated patients with invasive breast carcinoma (IBC). The associations between the levels of HER2-AAbs and breast cancer risk, and recurrence-free survival, were examined. High levels of HER2-AAbs were significantly associated with a reduced risk of DCIS (odds ratio [OR] 0.19, P = 4.6 × 10(-7)) or IBC (OR 0.31, P = 3.7 × 10(-7)). Subgroup analysis of IBC revealed a stronger association of HER2-AAbs with a reduced risk of the hormone receptor (HR)(-)/HER2(+) subtype (OR 0.12) than the other subtypes (HR(+)/HER2(-) [OR = 0.32], HR(+)/HER2(+) [OR 0.38], and HR(-)/HER2(-) [OR 0.29]). When we set the cutoff of HER2-AAbs at 20 ng/mL, recurrence-free survival of HER2-AAb-positive patients (N = 74) was significantly better than that of HER2-AAb-negative patients (N = 426) (P = 0.015). Univariate and multivariate analyses demonstrated that HER2-AAbs, as well as histological grade, were independently and significantly (P = 0.0065 and 0.049, respectively) associated with recurrence-free survival. Our exploratory study suggests a protective effect of naturally occurring HER2-AAbs on the development of primary and recurrent breast cancer. Further studies on HER2-AAbs are warranted.

Tumor-infiltrating B cells signal functional humoral immune responses in breast cancer

“…This study found that melanoma antigen-specific IgG4 antibodies impaired the ability of the corresponding IgG1 to induce antibody-dependent tumor cell phagocytosis. Alternatively, anti-HER2 autoantibodies have been associated with a protective effect for primary or recurrent BC development (73). Thus, polarization of Ig isotypes and/or subclasses is likely to have a significant impact on tumor immunity.…”

Combined detection of dickkopf-1 subtype classification autoantibodies as biomarkers for the diagnosis and prognosis of non-small cell lung cancer

“…The protective effect of DKK1 autoantibodies may be mediated by antitumor immunity. A previous report has shown that autoantibodies may promote antibody-dependent cellular cytotoxicity and induce antitumor immunity 33. Thus, we hypothesized that such immune responses against DKK1 epitopes may also impart a survival benefit.…”

Immune Responses to Epidermal Growth Factor Receptor (EGFR) and Their Application for Cancer Treatment

“…Humoral immune responses to HER2 have been extensively studied, and their clinical importance in a variety of cancers has been reported (Chapman et al, 2008; Knutson et al, 2016; Tabuchi et al, 2016). However, there have been limited information on humoral immune response to EGFR in cancer.…”

“…Immune responses to HER2, another molecule of the ErbB/HER onocogene family, have been well studied (Chapman et al, 2008; Knutson et al, 2016; Tabuchi et al, 2016), but only limited information on the immune responses to EGFR in cancer has been currently available. We have been studying cellular and humoral immune responses specific to EGFR (Yamada et al, 2013; Azuma et al, 2014a), as well as modulatory effect of EGFR-mediated signaling in expression of an immune checkpoint molecule, programmed death-ligand 1 (PD-L1) (Azuma et al, 2014b; Ota et al, 2015).…”