Discussion
cancer vaccine, chronic autoimmune disorders, death, tumor
TUMOR, BREAST CANCER
Neoadjuvant anthracyclines and taxanes still represent one standard-of-care therapy option in women with early, high-risk or locally advanced breast cancer [In the here presented study the stimulatory effects of D on soluble immunomodulatory biomarkers were clearly observable in vivo as well as in vitro. EC conversely led to a decrease of plasma levels of diverse soluble immunomodulatory molecules such as CXCL-10, uPA, suPAR, MCP-1, MCP-2 and Tweak in vivo and to decreasing levels in our in vitro experiments. Of note, we cannot clarify whether the effects of the initial four cycles of EC can be attributed either to E or C or to the combination of both. The alkylating agent C is a well-known immunosuppressant, commonly used to prevent graft rejection or to treat several chronic autoimmune disorders [In a recently published work Lopes et al. stated that the immune response is key to successful neoadjuvant chemotherapy [Limitations of our study were the retrospective nature of the study, the lack of long-term outcomes due to currently missing follow-up data as well as the division into subgroups depending on the NAC scheme, which led to a comparison of two smaller groups. With the intention to investigate the distinct effects of EC and D, ABCSG-34 patients receiving neoadjuvant AI therapy as well as all vaccinated patients were excluded. Reasons for this were the low risk profile of patients who were selected for neoadjuvant AI therapy in the ABCSG-34 trial and the unpredictable effect of the Mucin-1 cancer vaccine on circulating biomarkers and on sTILs or iTILs. Further, it has to be pointed out that the selection of immunomodulatory biomarkers was based on preliminary data from ABCSG-34 patients who received neoadjuvant AI therapy (see Supplementary Figure SAs chemotherapy, either in neoadjuvant or adjuvant manner, is frequently faced with tumor regrowth or drug resistance, a combination with immunotherapy seems promising. There is evidence that the form of cell death induction plays a pivotal role in the level of anti-tumor immune response. In the here presented study, a strong inhibitory effect of EC on lymphocytes was observed. This may counteract the stimulatory effect of immunotherapies, and thus, upfront taxane-therapy may be the preferred approach for trials of immunotherapeutic approaches in early-stage breast cancer.