Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case\u2013control study

Vesal Yaghoobi,Vasiliki Pelekanou,Myrto Moutafi,Tess O’Meara,Sanam Yaghoubi,Ioannis A Vathiotis,Aileen I Fernandez,Thazin Nwe Aung,Saba Shafi,Anup Sharma,Lajos Pusztai,Eiman Ibrahim,Kim Blenman,David L Rimm

doi:10.1186/s13058-021-01493-w

Vesal Yaghoobi, Vasiliki Pelekanou + Show 12 more

Open Access

https://doi.org/10.1186/s13058-021-01493-w

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Abstract

PurposeTriple negative breast cancer (TNBC) is more common in African American (AA) than Non-AA (NAA) population. We hypothesize that tumor microenvironment (TME) contributes to this disparity. Here, we use multiplex quantitative immunofluorescence to characterize the expression of immunologic biomarkers in the TME in both populations.Patients and methodsTNBC tumor resection specimen tissues from a 100-patient case: control cohort including 49 AA and 51 NAA were collected. TME markers including CD45, CD14, CD68, CD206, CD4, CD8, CD20, CD3, Ki67, GzB, Thy1, FAP, aSMA, CD34, Col4, VWF and PD-L1 we quantitatively assessed in every field of view. Mean expression levels were compared between cases and controls.ResultsAlthough no significant differences were detected in individual lymphoid and myeloid markers, we found that infiltration with CD45+ immune cells (p = 0.0102) was higher in TNBC in AA population. AA TNBC tumors also had significantly higher level of lymphocytic infiltration defined as CD45+ CD14− cells (p = 0.0081). CD3+ T-cells in AA tumors expressed significantly higher levels of Ki67 (0.0066) compared to NAAs, indicating that a higher percentage of AA tumors contained activated T-cells. All other biomarkers showed no significant differences between the AA and NAA group.ConclusionsWhile the TME in TNBC is rich in immune cells in both racial groups, there is a numerical increase in lymphoid infiltration in AA compared to NAA TNBC. Significantly, higher activated T cells seen in AA patients raises the possibility that there may be a subset of AA patients with improved response to immunotherapy.

Highlights

Results: no significant differences were detected in individual lymphoid and myeloid markers, we found that infiltration with C D45+ immune cells (p = 0.0102) was higher in Triple negative breast cancer (TNBC) in AA population
While the tumor microenvironment (TME) in TNBC is rich in immune cells in both racial groups, there is a numerical increase in lymphoid infiltration in AA compared to NAA TNBC
Higher activated T cells seen in AA patients raises the possibility that there may be a subset of AA patients with improved response to immunotherapy

Summary

Introduction

Solid tumor stroma is composed of many cell types including fibroblasts, immune cells (lymphocytes, macrophages, and myeloid derived stromal cells), and extracellular matrix (ECM). The cells and the signaling pathways in the tumor microenvironment (TME) resemble those associated wound healing suggesting that tumor stroma might be formed through abnormal activation of Yaghoobi et al Breast Cancer Research (2021) 23:113 wound healing pathways [1,2,3]. The TME in breast cancer, especially the basal-like subtype, appears to modulate tumor behavior. Experimental studies using ionizing radiation suggest that certain processes in the TME such as high immune function favor the development of ERnegative tumors [4,5,6,7]. The TME and secreted factors in breast tissue may be associated with the more basal-like breast tumors in these groups of patients [4,5,6,7]

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