The Prognostic Role of the Immune Microenvironment in Sinonasal Intestinal-Type Adenocarcinoma: A Computer-Assisted Image Analysis of CD3+ and CD8+ Tumor-Infiltrating Lymphocytes

Author:

Ferrari Marco123ORCID,Alessandrini Lara4,Savietto Enrico5ORCID,Cazzador Diego1,Schiavo Gloria1ORCID,Taboni Stefano126,Carobbio Andrea L. C.1,Calvanese Leonardo1ORCID,Contro Giacomo13,Gaudioso Piergiorgio1,Emanuelli Enzo5,Sbaraglia Marta4,Zanoletti Elisabetta1,Marioni Gino1ORCID,Dei Tos Angelo P.4,Nicolai Piero1

Affiliation:

1. Section of Otorhinolaryngology—Head and Neck Surgery, Department of Neurosciences, “Azienda Ospedale Università di Padova”, University of Padua, 35128 Padua, Italy

2. Guided Therapeutics (GTx) Program International Scholarship, University Health Network (UHN), Toronto, ON M5G1L7, Canada

3. Technology for Health (PhD Program), Department of Information Engineering, University of Brescia, 25123 Brescia, Italy

4. Section of Pathology, Department of Medicine, “Azienda Ospedale Università di Padova”, University of Padua, 35128 Padua, Italy

5. Unit of Otolaryngology, Hospital of Treviso AULSS 2-Marca Trevigiana, 31100 Treviso, Italy

6. Artificial Intelligence in Medicine and Innovation in Clinical Research and Methodology, Department of Clinical and Experimental Sciences, University of Brescia, 25100 Brescia, Italy

Abstract

The prognostic value of conventional histopathological parameters in the sinonasal intestinal-type adenocarcinoma (ITAC) has been debated and novel variables should be investigated. Increasing evidence demonstrated that the evolution of cancer is strongly dependent upon the complex interactions within tumor microenvironment. The aim of this retrospective study was to assess the features of immune microenvironment in terms of CD3+ and CD8+ cells in a series of ITAC and explore their prognostic role, as well as their relations with clinicopathological variables. A computer-assisted image analysis of CD3+ and CD8+ tumor-infiltrating lymphocytes (TIL) density was conducted on surgical specimens of 51 patients with ITAC that underwent a curative treatment including surgery. ITAC displays variable TIL density, which is associated with OS. In a univariate model, the density of CD3+ TIL was significantly related to OS (p = 0.012), whereas the association with CD8+ TIL density resulted in being non-significant (p = 0.056). Patients with intermediate CD3+ TIL density were associated with the best outcome, whereas 5-year OS was the lowest for intermediate CD8+ TIL density. CD3+ TIL density maintained a significant association with OS in the multivariable analysis. TIL density was not significantly related to demographic and clinicopathological variables. CD3+ TIL density was independently associated with OS in a non-linear fashion and patients with intermediate CD3+ TIL density had the best outcome. Though based on a preliminary analysis on a relatively small series of patients, this finding makes TIL density a potential independent prognostic factor of ITAC.

Publisher

MDPI AG

Subject

Medicine (miscellaneous)

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