Prognostic and predictive role of spatially positioned tumour infiltrating lymphocytes in metastatic HER2 positive breast cancer treated with trastuzumab

Abstract

Disease outcomes of HER2+ breast cancers have dramatically changed after targeted therapies, such as trastuzumab, came to clinical practice but predictive factors for trastuzumab sensitivity and resistance are frequently unknown. Current work included metastatic breast cancer patients (n = 48), who were treated with trastuzumab and had pre-treatment tumour samples available. The tumours were immunostained for T-cell (CD3, CD8), natural killer (NK)-cell (CD56) and macrophage (CD68) markers and quantitative analysis of the immune cells was carried out using a computer-assisted image analysis in different tumour locations. High number of CD3 and CD8 positive T-cells was associated with significant survival benefit in the center of the tumour (CT) (p = 0.007, p = 0.001) but not in the invasive margin. The number of NK-cells and macrophages in the CT showed non-significant tendency towards improved survival. In subgroup analyses, high density of CD8 CT cells was associated with significant survival benefit in non-bone only disease, in TX or T1-3, and in ER+ tumours (p = 0.006, p = 0.003, p = 0.001). Moreover, high CD8 CT cell density associated significantly with long trastuzumab interruption periods in response. The results suggest important prognostic and predictive role of tumour infiltrating lymphocytes in center of the tumours in metastatic HER2+ breast cancer.

A Novel Digital Score for Abundance of Tumour Infiltrating Lymphocytes Predicts Disease Free Survival in Oral Squamous Cell Carcinoma

“…The proposed framework for automated quantification of TILs, computation of their abundance score, and its prognostic analysis of patient survival using OSCC histology images is the first of its kind. Even though the total number of cases involved in this study is limited ( n = 70), some other studies have reported results on smaller cohorts 51 ( n = 48) or using tissue microarrays 52 (TMAs), which contain much smaller snapshots of tumour /lymphocytes characteristics as compared to the whole slide images. Having said that, the results of this study need to be cross-validated on data from large multi-centric patient cohorts before they can be adopted in clinical practice.…”

Effect of Estrogen Receptor Status on Circulatory Immune and Metabolomics Profiles of HER2-Positive Breast Cancer Patients Enrolled for Neoadjuvant Targeted Chemotherapy

“…In this context, the ER status was found associated with a differential expression of tumor infiltrating lymphocytes (TILs), raising the possibility of different immune-tumor interactions based on ER status [26][27][28]. Moreover, peripheral blood immune cells involved in antibody-dependent cell cytotoxicity (ADCC) and serum cytokines have been also associated to the trastuzumab response [29][30][31][32]. However, the association of response to NATC, as well as of disease relapse, with the ER status appears very elusive, requiring new stratification models to better identify the patients that can receive the best pharmacological benefit.…”

CD4 T-cell immune stimulation of HER2 + breast cancer cells alters response to trastuzumab in vitro

“…Limitations of this study include the lack of comparative data with CD8 + T-cells. CD8 + cytotoxic T-cells are observed to target cancerous tissue and patients with high CD8 + T-cell infiltration have a significant increase in survival [ 42 ]. TALL-104, a CD8 + T-cell cell line, can be used as a future direction to study CD8 + T-cell influence on trastuzumab treated HER2 + breast cancer [ 43 , 44 ].…”