Increased Tumour Infiltration of CD4+ and CD8+ T-Lymphocytes in Patients with Triple Negative Breast Cancer Suggests Susceptibility to Immune Therapy

Document Type: Research Articles

Authors

1 Department of Pathology, Dow International Medical College, Dow Diagnostic Research and Reference Laboratory, Dow University of Health Sciences Karachi, Pakistan.

2 Institute of Translational Immunology and Research Centre for Immunotherapy, Johannes Gutenberg University of Mainz, Germany.

Abstract

 
Background: Patients with triple negative breast cancer (TNBC) have limited therapeutic options, largely because the complex tumour environment is not well-characterized. These patients are potential, but largely un-fathomed, candidates for immunotherapy. It is therefore highly relevant to characterize leukocyte complexity in TNBCs. Objective: To investigate leukocyte complexity in tumour environment of patients with TNBCs. Materials and methods: A total of 104 consecutive breast cancer patients undergoing mastectomy were recruited in the study after ethical approval. Clinico-pathological parameters were recorded and H and E staining was performed to investigate tumour morphology. Receptor status was investigated using antibodies against ER, PgR and Her-2, and patients were classified as having TNBC or non-TNBC tumours (including Luminal A, Luminal B and Her2 overexpressing tumours). Immune-cell infiltration was investigated using special stains and antibodies: α-CD3 (T-lymphocytes), α-CD20 (B-lymphocytes), α-CD4 (helper T-lymphocytes) and α-CD8 (cytotoxic T-lymphocytes). Immune cell densities were quantified as cell/ mm2 using the CAP guidelines. Results: Of the 104 breast cancer patients investigated, a total of 27 (26%) had TNBC and 77(74%) non-TNBC. Patients with TNBC showed significantly increased tumour infiltration of lymphocytes (T and B-lymphocytes) compared to the patients with non-TNBC, while myelocytic infiltration was not significantly different in the two groups. Within the TNBC group, infiltration of T-lymphocytes (equal densities of CD4+ and CD8+ T-lymphocytes) was significantly higher compared to B-lymphocytes. Conclusion: Patients with TNBC show increased lymphocytic infiltration (more T-lymphocytes compared to B-lymphocytes). This suggests higher immunogenicity of TNBCs and may indicate a higher responsiveness of these cancers to immunotherapy.

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