Abstract 4075: Composition and distribution of tumor-infiltrating lymphocytes in breast cancer
Authors: Guo Liang , Chi Yayun , Xue Jingyan , Goswami Shyamal , Zhou Bingqing , Cao Chunmei , Shao Zhimin , Zhang Xiaoming , Wu Jiong 
Published: July 2016

Abstract
Backgroud: High tumor-infiltrating lymphocytes(TILs)are known to be associated with response to primary systemic therapy (PST) in breast cancer patients especially in Her2+ and triple negative patients. However, the composition of TILs in the high infiltration group is largely unknown. Uncovering the immunodynamic composition of TILs may be useful for better understanding the mechanism how the TILs exert effect. And the immune reservoir data for extensive analysis of altered TIL subsets after chemotherapy is still lacking.
Methods: The tumor specimens of 56 breast cancer patients who did not receive PST and 16 breast cancer patients who underwent surgical resection after anthracycline- or anthracycline/taxane-based PST were analysed. We used the multi -parametric flow cytometric platform (optimized for 20 colors for each panel of T cells, B cells, NK, and other Lineage markers detection) to accomplish the purpose. The result is more objective and estimated parameter is more abundant compared to the histological methods (hematoxylin-eosin staining and immunohistochemical staining). Breast cancer patients can be divided into low, medium and high infiltration group according to the CD45+ number in the tissue and weight of the tumor specimens. TIL subset composition is compared among different groups (Low vs Medium vs High, Chemotherapy vs non Chemotherapy).
Result: In patients with ER- and high histological grade patients, there are more TILs infiltration compared to the ER+ and low histological grade patients (P = 0.038 and P = 0.039 respectively). And we found that the percentage of CD4+T cells in total CD3+T cells, Treg in CD4+T cells and Plasmablasts in total B cells is much higher in the high infiltration group compared to the low infiltration group (56.03% vs 44.21%, P&lt;0.01; 18.64% vs 9.37%, P&lt;0.001; 16.75% vs 1.88%, P&lt;0.001 respectively). By contrast, percentage of CD8+T in total CD3+T cells and NK cells in the total lymphocytes is much lower (35.26% vs 46.71%, P&lt;0.001; 2.74% vs 5.88%, P&lt;0.01 respectively). After PST both the percentage of CD8+T in total CD3+T cells and effector memory CD8+T cells increase heavily (53.82% vs 41.14%, P&lt;0.001; 79.49% vs70.88%, P&lt;0.05 respectively) and percentage of CD4+T cells in total CD3+T and naïve CD8+T cells decrease (31.81% vs 50.35%, P&lt;0.001; 2.81% vs 4.21%, P&lt;0.05 respectively). Functional markers such as HLADR,CD28 and PD1 in the T cells decrease dramatically and CD127 increases noticeably.
Conclusion: The inner composition of TIL subsets in the high infiltration is largely different from low infiltration group and this might help explain the reason why high TILs could predict pathological complete response. Chemotherapy can lead to the heavy change of TIL subsets and this may be the part of immunological mechanism that why chemotherapy has deep influences on the tumor.
Citation Format: Liang Guo, Yayun Chi, Jingyan Xue, Shyamal Goswami, Bingqing Zhou, Chunmei Cao, Zhimin Shao, Xiaoming Zhang, Jiong Wu. Composition and distribution of tumor-infiltrating lymphocytes in breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4075.