Abstract 1604: Association of autoantibodies to HER2 with tumor microenvironments for humoral immunity and prognosis in patients with breast cancer
Authors: Shimoda Masafumi , Sato Yasufumi , Sota Yoshiaki , Miyake Tomohiro , Tanei Tomonori , Kagara Naofumi , Naoi Yasuto , Shimazu Kenzo , Kim Seung Jin , Noguchi Shinzaburo 
Published: September 2020

Abstract
AIM: We have previously reported that the serum concentration of anti-HER2 autoantibodies (HER2-AAb) is associated with favorable outcomes in patients with invasive breast cancer (Tabuchi et al., Breast Cancer Res Treat 157:55-63, 2016). This study aimed to investigate the prognostic impact of HER2-AAb by examining the tumor microenvironments for humoral immunity.
PATIENTS AND METHODS: From 500 consecutive patients with invasive breast cancer (Ibid.), we selected those whose log-transformed HER2-AAb values were above mean + 2SD (high HER2-AAb group, N = 33) or below mean − 2SD (low HER2-AAb group, N = 20). Tumor formalin-fixed paraffin-embedded (FFPE) samples and regional lymph node FFPE samples prepared from the patients’ surgical specimens were subjected to immunohistochemistry. Tumor-infiltrating immune cells (ICs) localized inside the tumor, in the adjacent stroma, and in the tumor stroma were separately counted. Expression of some proteins in tumor cells (TCs) was evaluated by the percentages of tumor cells showing presence of those proteins.
RESULTS: We confirmed in the selected patients that the recurrence-free interval of the high HER2-AAb group was significantly longer than that of the low HER2-AAb group (log-rank P = 0.017; hazard ratio = 0.12). Tumor-infiltrating CD20-positive ICs (intratumoral + adjacent stromal ICs, P &lt; 0.001), IGKC-positive ICs (intratumoral + adjacent stromal ICs, P = 0.023), and CXCL13-positive ICs (total ICs, P = 0.044) were significantly greater in the high HER2-AAb group than in the low HER2-AAb group. CD4-positive ICs in B-cell follicles of the regional lymph nodes were also significantly greater in the high HER2-AAb group than in the low HER2-AAb group (P = 0.026). Tumor-infiltrating PD-L1-positive ICs, CD8-positive ICs, FOXP3-positive ICs, as well as CD8/FOXP3 ratios, were not significantly different between the two groups. The expression of CXCL13, HLA-A/B/C, and PD-L1 in TCs was not significantly different between the two groups. The repertoire of B-cell receptors in ICs was not significantly different between the two groups but was considered to be skewed. HER2 expression and gene amplification and the existence of HER2 missense mutations were similar between the two groups.
CONCLUSIONS: Increased HER2-AAb concentration was associated with enhanced humoral immunity in tumor microenvironments. Our findings indicate that a patient subpopulation with enhanced humoral immunity protecting against breast cancer recurrence exists. The recognition site of HER2-AAb may not be located in the HER2 polypeptide, but may be located in modifying factors, such as sugar chains.
Citation Format: Masafumi Shimoda, Yasufumi Sato, Yoshiaki Sota, Tomohiro Miyake, Tomonori Tanei, Naofumi Kagara, Yasuto Naoi, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi. Association of autoantibodies to HER2 with tumor microenvironments for humoral immunity and prognosis in patients with breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1604.