1. NK Cell Infiltrates and HLA Class I Expression in Primary HER2 + Breast Cancer Predict and Uncouple Pathological Response and Disease-free Survival.
- Author
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Muntasell A, Rojo F, Servitja S, Rubio-Perez C, Cabo M, Tamborero D, Costa-García M, Martínez-Garcia M, Menéndez S, Vazquez I, Lluch A, Gonzalez-Perez A, Rovira A, López-Botet M, and Albanell J
- Subjects
- Biomarkers, Tumor, Breast Neoplasms diagnosis, Female, Gene Expression, Gene Expression Profiling, Histocompatibility Antigens Class I immunology, Histocompatibility Antigens Class I metabolism, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Prognosis, Receptor, ErbB-2 metabolism, Spain epidemiology, Breast Neoplasms etiology, Breast Neoplasms mortality, Histocompatibility Antigens Class I genetics, Killer Cells, Natural immunology, Killer Cells, Natural metabolism, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, Receptor, ErbB-2 genetics
- Abstract
Purpose: We investigated the value of tumor-infiltrating NK (TI-NK) cells and HLA class I tumor expression as biomarkers of response to neoadjuvant anti-HER2 antibody-based treatment in breast cancer., Experimental Design: TI-NK cells and HLA-I were determined by IHC in pretreatment tumor biopsies from two cohorts of patients with HER2-positive breast cancer [discovery cohort ( n = 42) and validation cohort ( n = 71)]. Tumor-infiltrating lymphocytes (TIL) were scored according to international guidelines. Biomarker association with pathologic complete response (pCR) and disease-free survival (DFS) was adjusted for prognostic factors. Gene set variation analysis was used for determining immune cell populations concomitant to NK-cell enrichment in HER2-positive tumors from the Cancer Genome Atlas ( n = 190)., Results: TI-NK cells were significantly associated with pCR in the discovery cohort as well as in the validation cohort ( P < 0.0001), independently of clinicopathologic factors. A ≥3 TI-NK cells/50x high-power field (HPF) cutoff predicted pCR in the discovery and validation cohort [OR, 188 (11-3154); OR, 19.5 (5.3-71.8)]. Presence of TI-NK cells associated with prolonged DFS in both patient cohorts [HR, 0.07 (0.01-0.6); P = 0.01; HR, 0.3 (0.08-1.3); P = 0.1]. NK-, activated dendritic- and CD8 T-cell gene expression signatures positively correlated in HER2-positive tumors, supporting the value of NK cells as surrogates of effective antitumor immunity. Stratification of patients by tumor HLA-I expression identified patients with low and high relapse risk independently of pCR., Conclusions: This study identifies baseline TI-NK cells as an independent biomarker with great predictive value for pCR to anti-HER2 antibody-based treatment and points to the complementary value of tumor HLA-I status for defining patient prognosis independently of pCR., (©2018 American Association for Cancer Research.)
- Published
- 2019
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