Tumor-infiltrating lymphocytes and CD8+ T cells predict survival of triple-negative breast cancer

H Vihervuori,H Repo,T A Autere,M M Lintunen,L Kallio,K Talvinen,P Kronqvist,S Kurki

doi:10.1007/s00432-019-03036-5

Abstract

PurposeTumor inflammatory response was evaluated as a prognostic feature in triple-negative breast cancer (TNBC) and compared with the clinical prognosticators of breast cancer and selected biomarkers of cancer cell proliferation.MethodsTNBC patients (n = 179) with complete clinical data and up to 18-year follow-up were obtained from Auria biobank, Turku University Hospital, Turku, Finland. Tumor-infiltrating lymphocytes (TILs) and several subtypes of inflammatory cells detected with immunohistochemistry were evaluated in different tumor compartments in full tissue sections and tissue microarrays.ResultsDeficiency of stromal TILs and low number of CD8+ T cells independently predicted mortality in TNBC (HR 2.4, p 0.02 and HR 2.1, p 0.02, respectively). Each 10% decrease in stromal TILs resulted in 20% increased risk of mortality. An average of 13.2-year survival difference was observed between the majority (> 75%) of patients with low (< 14% of TILs) vs high (≥ 14% of TILs) frequency of CD8+ T cells. The prognostic value of TILs and CD8+ T cells varied when evaluated in different tumor compartments. TILs and CD8+ T cells were significantly associated with Securin and Separase, essential regulators of metaphase–anaphase transition of the cell cycle.DiscussionTILs and CD8+ T cells provide additional prognostic value to the established clinical prognostic markers in TNBC. However, possible clinical applications would still benefit from systematic guidelines for evaluating tumor inflammatory response. Increasing understanding on the interactions between the regulation of cancer cell proliferation and inflammatory response may in future advance treatment of TNBC.

Highlights

Tumor microenvironment—the combination of neoplastic, inflammatory and pro-tumoral stromal cells and their associated soluble factors—conducts cellular interactions with crucial roles in malignancy (Monnot and Romero 2018)
Tumor-infiltrating lymphocytes (TILs) have been proposed with prognostic value in several malignancies, including melanomas and carcinomas of the upper and lower gastrointestinal tract (Balatoni et al 2018; Zheng et al 2017; Galon et al 2012)
The practical interpretation of our results is that each 10% decrease in the fraction of stromal TILs results in 20% increased risk of mortality in triple-negative breast cancer (TNBC), corresponding to findings in the previous literature (Loi et al 2014)

Summary

Introduction

Tumor microenvironment—the combination of neoplastic, inflammatory and pro-tumoral stromal cells and their associated soluble factors—conducts cellular interactions with crucial roles in malignancy (Monnot and Romero 2018). Of particular interest is the inflammatory cell component which, depending on the immunogeneity of the neoplasm, may be involved in complicated tumor-promoting or -suppressing. Inflammatory cells may either suppress tumor growth through destruction of malignant cells or, establish an immunosuppressive microenvironment which favors escape of the tumor cells from the anti-tumoral immune response (da Silva et al 2019). Reflecting the versatile involvement of immune response in malignancy, inflammatory cells have been reported with numerous and partly discrepant roles in different types of tumors. Specific subtypes of inflammatory cells and their impact on disease survival and treatment response have been described in different subtypes of breast cancer (Yang et al 2018).

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