Prognostic and Predictive Significance of Stromal Tumor-Infiltrating Lymphocytes (sTILs) in ER-Positive/HER2-Negative Postmenopausal Breast Cancer Patients

Jenny Pousette; Annelie Johansson; Carolin Jönsson; Tommy Fornander; Linda S Lindström; Hans Olsson; Gizeh Perez-Tenorio

doi:10.3390/cancers14194844

Prognostic and Predictive Significance of Stromal Tumor-Infiltrating Lymphocytes (sTILs) in ER-Positive/HER2-Negative Postmenopausal Breast Cancer Patients

Cancers (Basel). 2022 Oct 4;14(19):4844. doi: 10.3390/cancers14194844.

Authors

Jenny Pousette^{1

2}, Annelie Johansson³, Carolin Jönsson^{1

2}, Tommy Fornander³, Linda S Lindström³, Hans Olsson^{1

4}, Gizeh Perez-Tenorio^{1

2}

Affiliations

¹ Department of Biomedical and Clinical Sciences, Linköping University, 581 83 Linköping, Sweden.
² Department of Oncology, Linköping University, 581 83 Linköping, Sweden.
³ Department of Oncology and Pathology, Karolinska Institute and University Hospital, 171 64 Stockholm, Sweden.
⁴ Department of Molecular and Immunological Pathology, Linköping University, 581 83 Linköping, Sweden.

Abstract

The clinical impact of tumor-infiltrating lymphocytes (TILs) is less known for breast cancer patients with the estrogen receptor-positive (ER+)/human epidermal growth factor receptor-negative (HER−) subtype. Here, we explored the prognostic and predictive value of TILs regarding distant recurrence-free interval (DRFI) and breast cancer-specific survival (BCSS) in 763 postmenopausal patients randomized to receive tamoxifen vs. no systemic treatment. TILs were assessed in whole section tumor samples stained with H&E and divided into low (<10%), intermediate (10−39%), or high (≥40%). High TILs were associated with poor prognostic variables and good prognoses for all patients, but not within the ER+/HER2− group. Within the ER+/HER2− group, high gene expression of CD19 and PD-L1 and high IMMUNE1 score indicated good prognosis in multivariable analysis while high CD8 and CD19 gene expression and high IMMUNE1 score were associated with less tamoxifen benefit. These results indicate that within the ER+/HER2− subtype there could be subsets of patients where expression of specific TIL markers might be used to reveal candidates for immune therapy interventions upon failure of the endocrine therapy.

Keywords: B-lymphocytes; T-lymphocytes; anti-tumoral response; endocrine treatment; immune checkpoint blockade; immune response.

Grants and funding

This work was supported by the Swedish Research Council (Vetenskapsrådet, grant number 2020-02466 to L.S.L); the Swedish Research Council for Health, Working life and Welfare, (FORTE, grant number 2019-00477 to L.S.L); the Gösta Milton Donation Fund (Stiftelsen Gösta Miltons donationsfond, to L.S.L and G.P.T); the Swedish Cancer Society (Cancerfonden, grant number 190140 and 220552SIA to L.S.L); Stockholm Cancer Society (Cancerföreningen i Stockholm, grant number 201212 to L.S.L); Svenska Läkarecellskapet (SLS to G.P.T).