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A high CD8 to FOXP3 Ratio in The Tumor Stroma is Associated with Improved Survival in Non-Metastatic Triple-Negative Breast Carcinoma

Monique C. Tavares* , Cristina D. A. T. Sampaio, Geraldine E. de Lima, Victor P. de Andrade; Daniel G. Goncalves, Mariana P. de Macedo, Vladmir C. Cordeiro de Lima

Triple-Negative Mammary Carcinoma (TNBC) is an aggressive breast cancer subtype associated with dismal prognosis. The interaction between the immune system and the cancer cells plays a crucial role in tumor development and progression. However, it is still unclear how each diverse cell of the immune system contributes to the prognosis of patients with breast cancer. Purpose: In this study, we investigated how the cell composition of the immune cell infiltrated modifies the survival of patients with resected TNBC. Methods: Retrospectively, we collected data from 76 patients diagnosed with non-metastatic TNBC with available tissue blocks for Tissue Micro-Array (TMA) construction. The TMA was constructed using two cores from each tumor block. The expression of CD4, CD8, FOXP3, CD20, CD68, CD163, PD-1, PD-L1, PTEN and phosphoSTAT1 was determined by immunohistochemistry. Results: We observed that the inflammatory infiltrate in TNBC is enriched for M2 macrophages and T lymphocytes (CD4+ , CD8+ and FOXP3+ ). We found a correlation between TIL and PD-L1 expression in stroma cells (p=0.001) and in tumor cells (p=0.028). There was no association between PD-L1 expression and OS. The number of FOXP3+ cells and the lack of expression of PTEN in tumor cells were associated with OS. Conclusion: We did not observe any association CD8 and CD4 cell counts in the tumor and survival, however a higher CD8/FOXP3 ratio was associated with improved survival. This was confirmed in the METABRIC TNBC cohort, where a high CD8A to FOXP3 gene expression ratio was also associated with longer survival.