Abstract
Background. Intestinal-type adenocarcinoma (ITAC) is a rare tumour occurring in the ethmoid sinus. Recent years have brought advances in endoscopic surgery and precision radiotherapy; however, five-year overall survival has not improved and remains at 35–80%, depending on tumour stage and histology. Therefore, there is a need for new therapeutic options. Methods. We evaluated CD8+ tumour-infiltrating lymphocytes (TILs) and tumour microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) as predictive biomarkers for immunotherapy in a series of 133 ITAC. All results were correlated to clinical and follow-up data. Results. The presence of intratumoural CD8+ TILs was low in 57% of cases and high in 8% of cases. Tumoural PD-L1 positivity was observed in 26% of cases. CD8+ TILs and TMIT correlated with the histological subtype of ITAC and with better overall survival. The presence of stromal PD-L1-positive macrophages was related to intratumoural CD8+ TILs. PD-L1 expression on tumour cells or macrophages did not show prognostic value. Conclusions. TMIT classification did not have additional prognostic value over CD8+ TILs alone. The modest percentage of CD8high/PD-L1pos cases indicates that ITAC is a lowly immunogenic tumour type. Nevertheless, a proportion of ITAC, especially the papillary and colonic subtypes, could benefit from therapy with immune checkpoint inhibitors.
Highlights
Intestinal-type adenocarcinoma (ITAC) is a rare tumour, with an approximate incidence of less than one case per 100,000 inhabitants annually, accounting for 10–20% of all tumours in the sinonasal area, these proportions vary geographically [1,2,3]
By analysing Programmed death-ligand 1 (PD-L1) staining for the evaluation of TMIT, we found 26% (35/133) of cases with clinical and follow-up data (Table positivity in patches of tumour cells, and this was positively correlated (p = 0.000) with intratumoural presence of CD8+ tumour-infiltrating lymphocytes (TILs) (Table 3)
We compared cases treated before and after the year 2003, the point in time when endoscopic surgery was introduced in our hospital, and we found the same distribution of CD8+ TILs and TMIT types and the same association with overall survival
Summary
Intestinal-type adenocarcinoma (ITAC) is a rare tumour, with an approximate incidence of less than one case per 100,000 inhabitants annually, accounting for 10–20% of all tumours in the sinonasal area, these proportions vary geographically [1,2,3]. The main treatment modality is surgery with postoperative radiotherapy, and in some cases combined modalities including chemotherapy may be used. Intestinal-type adenocarcinoma (ITAC) is a rare tumour occurring in the ethmoid sinus. Recent years have brought advances in endoscopic surgery and precision radiotherapy; five-year overall survival has not improved and remains at 35–80%, depending on tumour stage and histology. CD8+ tumour-infiltrating lymphocytes (TILs) and tumour microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) as predictive biomarkers for immunotherapy in a series of 133 ITAC.
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