Prognostic implications of tumor-infiltrating T cells in early-stage endometrial cancer

• Published in: Modern pathology 2022-02, Vol.35 (2), p.256-265
• Main Authors: Mendiola, Marta, Pellinen, Teijo, Ramon-Patino, Jorge L., Berjon, Alberto, Bruck, Oscar, Heredia-Soto, Victoria, Turkki, Riku, Escudero, Javier, Hemmes, Annabrita, Garcia de la Calle, Luis E., Crespo, Roberto, Gallego, Alejandro, Hernandez, Alicia, Feliu, Jaime, Redondo, Andres
• Format: Article
• Language: English
• Subjects: 13/1; 14/105; 14/35; 14/63; 631/67/1517; 692/53/2422; 692/699/67; 82/80; B7-H1 Antigen; Carcinoma; CD25 antigen; CD3 antigen; CD4 antigen; Cytotoxicity; Endometrial cancer; Endometrial Neoplasms - pathology; Endometrium; Female; Humans; Immunohistochemistry; Laboratory Medicine; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating; Medicine; Medicine & Public Health; Metastases; Neoplasm Recurrence, Local - pathology; Pathology; PD-1 protein; PD-L1 protein; Prognosis; Stromal cells; Tumor-infiltrating lymphocytes; Uterine cancer
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/s41379-021-00930-7

Patients with endometrial cancer differ in terms of the extent of T-cell infiltration; however, the association between T-cell subpopulations and patient outcomes remains unexplored. We characterized 285 early-stage endometrial carcinoma samples for T-cell infiltrates in a tissue microarray format using multiplex fluorescent immunohistochemistry. The proportion of T cells and their subpopulations were associated with clinicopathological features and relapse-free survival outcomes. CD3+ CD4+ infiltrates were more abundant in the patients with higher grade or non-endometrioid histology. Cytotoxic T cells (CD25+, PD-1+, and PD-L1+) were strongly associated with longer relapse-free survival. Moreover, CD3+ PD-1+ stromal cells were independent of other immune T-cell populations and clinicopathological factors in predicting relapses. Patients with high stromal T-cell fraction of CD3+ PD-1+ cells were associated with a 5-year relapse-free survival rate of 93.7% compared to 79.0% in patients with low CD3+ PD-1+ fraction. Moreover, in patients classically linked to a favorable outcome (such as endometrioid subtype and low-grade tumors), the stromal CD3+ PD-1+ T-cell fraction remained prognostically significant. This study supports that T-cell infiltrates play a significant prognostic role in early-stage endometrial carcinoma. Specifically, CD3+ PD-1+ stromal cells emerge as a promising novel prognostic biomarker.