Abstract 4376: A correlation of soluble HLA serum levels with clinical data and survival in patients with invasive breast cancer after neoadjuvant treatment
Authors: Tegeler Christian M. , Rieth Jonas , Koch André , Dannehl Dominik , Volmer Léa L. , Matovina Sabine , Hahn Markus , Engler Tobias , Hartkopf Andreas D. , Brucker Sara Y. , Walz Juliane S. , Heitmann Jonas S. , Nelde Annika 
Published: April 2023

Abstract
Invasive breast cancer (IBC) is the most common malignant disease in women worldwide. In recent years, the landscape of treatment options has rapidly evolved. With the success of checkpoint inhibitors in triple negative IBC, immunotherapy has become standard of care highlighting the strength of T cell-based strategies for anti-tumor therapy. Naturally, the targets of T cell-mediated immune responses are represented by short peptides presented on human leukocyte antigen (HLA) molecules. For several years, huge effort has been made to analyze and characterize HLA-presented tumor antigens to further understand anti-tumor immunity and to identify suitable targets for novel immunotherapy approaches. Aside from membrane-bound HLA molecules, soluble HLA-peptide complexes (sHLA) can be found in a variety of body fluids. These molecules are suggested to impact cellular immune responses, but it is still a matter of debate, whether shifts in sHLA levels contribute to disease outcome or are observed as a consequence of disease. Whereas the role of the non-classical sHLA-G in IBC has been studied showing elevated levels in patients compared to a healthy cohort, data on classical sHLA class I molecules is not yet available. Here, we report on sHLA class I serum levels in patients with IBC after neoadjuvant chemotherapy or combined chemotherapy with antibody treatment (n = 52). We observed higher serum levels of sHLA in neoadjuvant-treated IBC patients without histopathological complete response after neoadjuvant therapy (n = 36) compared to healthy volunteers (n = 84). Patients with locally advanced tumors, according to TNM classification, had a tendency towards lower sHLA levels than patients with small size tumors. Furthermore, sHLA levels were decreased in patients with sentinel node or disseminated axillary lymph node metastases compared to non-metastatic patients. Of note, sHLA levels tended to be elevated in patients with Her2-overexpression (based on immunohistochemistry staining and fluorescence in situ hybridization), whereas for histological hormone receptor expression a tendency towards lower sHLA levels in patients with high expression was observed. Furthermore, sHLA levels were reduced in patients with disseminated tumor cells in bone marrow aspiration. No significant difference in sHLA levels were seen in terms of grading of tumor, prevalence of distant metastasis, menopausal status and elevated tumor markers. Interestingly, we observed a tendency to prolonged progression-free survival in patients with high serum concentrations of sHLA, which will be updated with data from additional patients at the AACR meeting. Taken together, these data provides first insights about sHLA class I in patients with IBC after neoadjuvant treatment suggesting an impact of sHLA and T cell-mediated immune surveillance on survival in patients with IBC.
Citation Format: Christian M. Tegeler, Jonas Rieth, André Koch, Dominik Dannehl, Léa L. Volmer, Sabine Matovina, Markus Hahn, Tobias Engler, Andreas D. Hartkopf, Sara Y. Brucker, Juliane S. Walz, Jonas S. Heitmann, Annika Nelde. A correlation of soluble HLA serum levels with clinical data and survival in patients with invasive breast cancer after neoadjuvant treatment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4376.