10.3389/fonc.2020.00968.s002
Douglas K. Marks
Douglas K.
Marks
Robyn D. Gartrell
Robyn D.
Gartrell
Margueritta El Asmar
Margueritta El
Asmar
Shuobo Boboila
Shuobo
Boboila
Thomas Hart
Thomas
Hart
Yan Lu
Yan
Lu
Qingfei Pan
Qingfei
Pan
Jiyang Yu
Jiyang
Yu
Hanina Hibshoosh
Hanina
Hibshoosh
Hua Guo
Hua
Guo
Eleni Andreopoulou
Eleni
Andreopoulou
Lisa Wiechmann
Lisa
Wiechmann
Katherine Crew
Katherine
Crew
Joseph Sparano
Joseph
Sparano
Dawn Hershman
Dawn
Hershman
Eileen Connolly
Eileen
Connolly
Yvonne Saenger
Yvonne
Saenger
Kevin Kalinsky
Kevin
Kalinsky
Image_2_Akt Inhibition Is Associated With Favorable Immune Profile Changes Within the Tumor Microenvironment of Hormone Receptor Positive, HER2 Negative Breast Cancer.TIF
Frontiers
2020
breast cancer
tumor microenvironment
MK-2206
AKT inhibitor
quantitative multiplex immunofluorescence
tumor immunobiology
pre-surgical
2020-06-16 04:20:57
Figure
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
<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>