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

Abstract

<br /> <strong><span style="font-size: small;">Background: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">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. </span></span><strong><span style="font-size: small;">Objective: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">To investigate leukocyte complexity in tumour environment of patients with TNBCs. </span></span><strong><span style="font-size: small;">Materials and methods: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">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. </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Receptor status was investigated using antibodies against ER, PgR and Her-2, and patients were classified as having </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">TNBC or non-TNBC tumours (including Luminal A, Luminal B and Her2 overexpressing tumours). Immune-cell </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">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/ </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">mm</span></span>^{<span style="font-family: Times New Roman,Times New Roman; font-size: xx-small;"><span style="font-family: Times New Roman,Times New Roman; font-size: xx-small;">2 </span></span>}<span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">using the CAP guidelines. </span></span><strong><span style="font-size: small;">Results: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Of the 104 breast cancer patients investigated, a total of 27 (26%) had TNBC </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">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. </span></span><strong><span style="font-size: small;">Conclusion: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Patients with TNBC show increased </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">lymphocytic infiltration (more T-lymphocytes compared to B-lymphocytes). This suggests higher immunogenicity of </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">TNBCs and may indicate a higher responsiveness of these cancers to immunotherapy. </span></span>