A low number of tumor infiltrating FOXP3-positive cells after primary systemic chemotherapy is correlated with favorable relapse-free survival in breast cancer patients.
Authors: Aruga T , Suzuki E , Horiguchi S , Horiguchi K , Sekine S , Kitagawa D , Saji S , Funata N , Toi M , Kuroi K 
Published: December 2010

Abstract #5043

Background: Cancer cells induce proliferation and local accumulation of immunosuppressive cells such as FOXP3-positive cells which known as regulatory T cells (Tregs). Tregs prevent the maturation of dendritic cells and their capacity to present tumor antigens to cytotoxic T lymphocytes (CTLs) and leads to tumor-induced tolerance. Although cancer chemotherapy was usually considered as immunosuppressive, some chemotherapeutic agents have recently been shown to activate an anticancer immune response, which is involved in the curative effect of these treatments. Therefore, we hypothesized that number of tumor infiltrating FOXP3-positive cells during primary systemic chemotherapy is correlated with therapeutic results in breast cancer patients.&#x2028; Methods: To test the hypothesis, between September 2000 and January 2005, breast cancer patients treated with primary systemic chemotherapy (PSC) (n=93) were included in the study. Three cases were excluded because main tumors were resected before PSC and three cases of pathological complete reaction were excluded because they were hard to define “tumor infiltrating” Tregs. To compare the number of FOXP3 positive cells in the tumors before and after PST, both core-needle biopsy (CNB) and surgical resected specimens were stained with FOXP3 monoclonal antibody. Numbers of tumor infiltrating FOXP3-positive cells were counted in 3 and 5 randomly chosen high power fields (CNB and surgical specimens, respectively). A median cutoff of &gt;16.3 and &gt; 6.6 defined patients with high numbers of Tregs (CNB and surgical specimens, respectively). We also divided the patients into four groups (high numbers of FOXP3 positive cells in both CNB and surgical specimens; HH, low numbers in the both specimens; LL, high numbers in CNB and low in the surgical specimens; HL, and low in CNB and high in surgical specimens; LH). All patients were treated with anthracyclin containing therapy and 79.3 %( n=69) of them were added taxanes sequentially.&#x2028; Results: In the tumors after PST, numbers of Tregs were significantly higher in lymphvessel invasion positive tumors (P=0.01) and ER negative tumors (P=0.02) but there was no correlation between lymph node involvement and numbers of Tregs (P=0.8). As for the comparison of four groups, LL group shows the longest relapse-free (P=0.04) and overall survival (P=0.09) and HH group shows the shortest relapse-free and overall survival among four groups. Interestingly, HL group shows better outcome than HH group and LH group shows worse one than LL.&#x2028; Conclusions: These findings suggest that the control of Tregs in the tumor is important for the control of the disease and Tregs might be an important therapeutic target for breast cancer. Furthermore, it is suggested that some chemotherapeutic agents could be a potential inhibitor of the Tregs in tumor and show antitumor effects addition to their direct cytotoxicity against cancer cells.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5043.