Abstract P4-06-12: Biological characteristics and prognostic value of Tfh-like cells in the tumor tissue of breast cancer
Authors: L-X Ma, L Guo, S Goswami, T Li, C-M Cao, X-m Zhang, J Wu
Journal: Cancer Research (2019)

Abstract Objective T follicular helper (Tfh) cells formed in germinal center are a distinct subpopulation of CD4+ T cell, with high levels of CXCR5, ICOS, PD-1, Bcl-6 and CXCL13 as their characteristic markers. Secreting IL-21 and helping humoral response are their key features. They have been identified in different types of tumors. However, it still remains unclear in breast cancer. Researches of them may provide new clues to the diagnosis and treatment of breast cancer, especially for the potential immunotherapies. This study was performed to explore the existence and a possible role of Tfh cells in breast cancer. Method Freshly resected invasive breast cancer tissue from Fudan University Shanghai Cancer Center (FUSCC) were collected, with 27 samples for identifying the presence, phenotype and cytokine-producing capacity of Tfh-like cells and 386 for exploring the correlation between Tfh-like cells and clinicopathological characteristics in breast cancer during 03/2015 to 05/2017. Of all those 386 samples, patients were divided into Luminal A (N=61), Luminal B (HER2-) (N=138), Luminal B (HER2+) (N=72), HER2+ (non-luminal) (N=57) and triple negative (N=58) based on St Gallen International Expert Consensus. Data was analyzed based on the result from Multiparameter Flow Cytometry. The correlation between Tfh-like cells and clinicopathological characteristics in breast cancer was examined with t test or one way ANOVA with Tukey's multiple comparisons test. Results A subpopulation of PD1hiCD4+ T cells in tumor tissues of breast cancer was identified as Tfh-like cells, with the specific expression of Bcl-6 and CXCL13. Phenotypes of those cells were checked by flow cytometry. They were of a high level of ICOS but negative for CXCR5, suggesting that they were atypical Tfh cells. They had high levels of activated molecules such as CD38, CD71, CD95 and HLADR, showing that they were highly activated. They had high levels of suppressive markers as Tim3, TIGIT, and LAG3, indicating they could have regulatory functions. In addition, Tfh-like cells specifically secreted cytokine IL-21 with stimulation. Data showed that high grade (N=166; mean±SEM, 17.62±0.87) compared with low grade (N=220; mean±SEM, 12.41±0.46) or high Ki-67 level (N=300; mean±SEM, 15.38±0.58) with low Ki-67 level (N=86; mean±SEM, 12.10±0.67), and negative ER expression (N=115; mean±SEM, 17.47±1.05) compared with positive ER expression (N=271; mean±SEM, 13.46±0.50) or negative PR expression (N=177; mean±SEM, 16.87±0.83) compared with positive PR expression (N=209; mean±SEM, 12.77±0.50) was associated with higher frequency of Tfh-like cells (P&amp;lt;0.01 to all). Patients with triple negative had higher frequency of Tfh-like cells than those with Luminal A (difference, 6.83; P=0.0006) and Luminal B (HER2-) (difference, 4.61; P=0.0124). Patients with HER2+ (non-luminal) had higher frequency of Tfh-like cells than those with Luminal A (difference, 5.34; P=0.0146). These results indicate that higher frequency of Tfh-like cells could have negative prognostic influence. Conclusion Our study defined a PD1hiBcl6+CXCL13+CD4+ T cell subpopulation, which specifically secretes cytokine IL-21 as Tfh-like cells. Higher frequency of Tfh-like cells is more likely to be seen in patients with poor prognosis. Citation Format: Ma L-X, Guo L, Goswami S, Li T, Cao C-M, Zhang X-m, Wu J. Biological characteristics and prognostic value of Tfh-like cells in the tumor tissue of breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-12.