[Profile and immune environment of upper tract urothelial carcinoma]

Abstract

Introduction and objectives: Upper Tract Urothelial Carcinoma (UTUC) are tumors that share similarities with bladder tumors. Immunotherapy is already used for bladder locations and appears to have interest for UTUC. In order to rationalize the immunotherapy development pipeline it seemed necessary to describe the immune infiltrate of a cohort of UTUC treated with nephroureterectomy and to determine the expression of a panel of immune checkpoints and co-stimulatory molecules on tumor cells as well as on infiltrating and circulating lymphocytes.

Materials and methods: This is a monocentric, prospective and exploratory work. Patients treated with total nephroureterectomy or segmental ureterectomy for presumably infiltrative (≥ T1) UTUC managed at the Saint-Louis Hospital were included from January 2019 to July 2020. A set of markers and immune checkpoints were studied by flow fluorocytometry on circulating lymphocytes (PBMCs) and tumor-infiltrating lymphocytes (TILs). Some markers were also studied by immunohistochemistry on tumor sample.

Results: In total, 14 patients were included and 13 patients could be analyzed. 1 patient had no residual tumor. 5 tumors out of the 12 (41.7%) showed a lymphocytic inflammatory infiltrate. PD1 was the most represented checkpoint with a median expression rate of 41.4% on CD4+ TILs and 3.89% on circulating CD4+ T cells. This rate was 62.4% and 7.45% respectively on CD8+ T cells. TIGIT was the second most represented marker with a median expression rate on tumor-infiltrating CD4+ T cells of 25% and 2.9% on circulating CD4+ T cells. The median expression level of TIGIT on tumor-infiltrating CD8+ T cells was 23.3% and 3.2% on circulating CD8+ T cells. ICOS was highly expressed on CD4+ TILS with a median of 33.9% in contrast to CD8+ TILS (median: 6.67%). Variable expression of other checkpoints (ILT2, TIM3, LAG3 and OX40) was found without clear trend.

Conclusion: This exploratory work highlighted that PD1 was the most represented checkpoint. TIGIT was the second most represented checkpoint while ICOS, TIM3 and LAG3 were 3 other checkpoints whose expression was found to be less important. ILT2 and OX40 appeared to be weakly expressed.

Level of evidence: II.

Keywords: Checkpoint immunitaires; Immune checkpoints; PD-L1; PD1; Tumeurs de la voie excrétrice supérieure; Upper tract uothelial carcinoma.