Emerging Scholars

Endometrial cancer is the most common cancer of the female reproductive organs. It is classified into four molecular subtypes of which the p53 abnormal variant is biologically aggressive. Programmed cell death protein 1 (PD-1) is a cell surface receptor and a vital inhibitor of the immune response. Programmed death ligand 1 (PD-L1) is a trans-membrane co-inhibitory factor of the immune response. Some cancer cells express PD-L1, which then binds to PD-1 expressed on tumor specific T cells, and escape destruction by the T cells. The CD4/CD8 T cell immune response in the p53 abnormal variant has not been adequately evaluated with respect to the PD-1/PD-L1 pathway. Understanding this immune microenvironment is important to assess the potential use of anti-PD-1 targeted tumor therapy. Twenty cases of PDL-1 positive p53 abnormal endometrial cancers were studied using dual stain immunohistochemistry for CD4/PD-1 and CD8/PD-1. A statistically significant increase in the number of CD8 +ve cells compared to CD4 +ve cells was seen in the tumor microenvironment (p=0.0023). Conversely, the percentage of PD-1/CD4 +ve cells was higher compared to the percentage of PD-1/CD8 +ve cells, achieving statistical significance (p=0.0116). The statistically significant increase in CD8 cells in the tumor and its stroma suggests that a robust cytotoxic response is being mounted to this high-risk molecular variant. The concurrent increase in CD4/PD-1 positive lymphocytes provides an appropriate microenvironment for the use of anti-PD-1 immunotherapy since blockade of PD-1 on CD4 helper T cells may augment the cytotoxic properties of the CD8 positive lymphocytes.    

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