Marks, Douglas K. Gartrell, Robyn D. Asmar, Margueritta El Boboila, Shuobo Hart, Thomas Lu, Yan Pan, Qingfei Yu, Jiyang Hibshoosh, Hanina Guo, Hua Andreopoulou, Eleni Wiechmann, Lisa Crew, Katherine Sparano, Joseph Hershman, Dawn Connolly, Eileen Saenger, Yvonne Kalinsky, Kevin Image_2_Akt Inhibition Is Associated With Favorable Immune Profile Changes Within the Tumor Microenvironment of Hormone Receptor Positive, HER2 Negative Breast Cancer.TIF <p>Background: The PI3K/Akt/mTOR pathway in part impacts tumorigenesis through modulation of host immune activity. To assess the effects of Akt inhibition on the tumor micro-environment (TME), we analyzed tumor tissue from patients with operable hormone receptor positive, HER2 negative breast cancer (BC) treated on a presurgical trial with the Akt inhibitor MK-2206.</p><p>Methods: Quantitative multiplex immunofluorescence (qmIF) was performed using CD3, CD8, CD4, FOXP3, CD68, and pancytokeratin on biopsy and surgical specimens of MK-2206 and untreated, control patients. nanoString was performed on surgical specimens to assess mRNA expression from MK-2206-treated vs. control patients.</p><p>Results: Increased CD3+CD8+ density was observed in post vs. pre-treatment tissue in the MK-2206-treated vs. control patients (87 vs. 0.2%, p < 0.05). MK-2206 was associated with greater expression of interferon signaling genes (e.g., IFI6, p < 0.05) and lower expression of myeloid genes (CD163, p < 0.05) on differential expression and gene set enrichment analyses. Greater expression of pro-apoptotic genes (e.g., BAD) were associated with MK-2206 treatment (p < 0.05).</p><p>Conclusion: Akt inhibition in operable BC was associated with a favorable immune profile in the TME, including increased CD3+CD8+ density and greater expression of interferon genes. Additional studies are warranted, as this may provide rationale for combining Akt inhibition with immunotherapy.</p> breast cancer;tumor microenvironment;MK-2206;AKT inhibitor;quantitative multiplex immunofluorescence;tumor immunobiology;pre-surgical 2020-06-16
    https://frontiersin.figshare.com/articles/figure/Image_2_Akt_Inhibition_Is_Associated_With_Favorable_Immune_Profile_Changes_Within_the_Tumor_Microenvironment_of_Hormone_Receptor_Positive_HER2_Negative_Breast_Cancer_TIF/12487709
10.3389/fonc.2020.00968.s002