CD8+ Tumour-Infiltrating Lymphocytes and Tumour Microenvironment Immune Types as Biomarkers for Immunotherapy in Sinonasal Intestinal-Type Adenocarcinoma

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.

Prognostic and Therapeutic Implications of Immune Classification by CD8+ Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma

“…This result suggests that SNSCCs are immunogenic tumors and is in agreement with the previously published studies on SNSCCs and HNSCCs reporting CD8 + TILs in 35-50% of cases [15][16][17][18][19][20][21]. In contrast, in ITACs and low-grade ONBs, two other tumor types of the sinonasal region, CD8 + TILs were much less frequent and were predominantly found in the stromal compartment [22,23,29].…”

“…These two factors are reflected in TMIT I (CD8 high /PD-L1 pos ), which we observed in 19% of the SNSCCs, very similar to the 23% found by Quan et al [20]. This proportion is lower than in highly immunogenic tumors such as melanomas, renal cell and bladder cancers, HNSCCs or lung squamous cell carcinomas (40-50% of the cases belong to TMIT I) [25], but still higher than in other sinonasal cancers such as ITACs and ONBs [22,23,29].…”

“…Classifying our series of SNSCCs according to the TMIT did not yield additional prognostic information; TMIT I (CD8 high ) presented worse survival compared to TMITs II and III (both CD8 low ). This result contrasts with reports on other sinonasal tumors, including SNSCCs, ITACs, ONBs [15,[21][22][23]29] and histologically similar HNSCCs [17][18][19]25]. In fact, a positive relation between high CD8 + TIL scores and favorable prognosis is found in the majority of cancer types such as ovarian [30], renal [31], lung [32] and pancreatic cancers [33], although a number of studies have found high CD8 + TIL scores related to worse survival [34][35][36].…”

“…Previous studies reported 30-34% PD-L1 expression in SNSCCs, indicating a subgroup of patients that may benefit from immunotherapy [14,15]. The presence of CD8 + TILs has been associated with favorable clinical outcomes in patients with HNSCCs [15][16][17][18][19][20][21] and also in sinonasal tumors including SNSCCs, intestinal type adenocarcinomas (ITAC) and olfactory neuroblastomas (ONB) [15,22,23]. Tumor microenvironment immune type (TMIT) is a classification recognizing four immunotypes based on the presence of intratumoral CD8 + TILs and tumoral PD-L1 expression [24,25].…”

Complete response to immunotherapy in sinonasal undifferentiated carcinoma

“…3 There is limited evidence about the expression of PD-L1 and TIL in sinonasal cancers, mainly reported in intestinal-type adenocarcinoma and in sinonasal squamous cell carcinoma, but no SNUCs have been studied in this regard. [9][10] Until now, to our knowledge, only 2 cases of sinonasal cancers, not undifferentiated carcinoma, treated with immunotherapy have been reported, concurrently with radiation. 11 The present case adds to the literature the experience of a long-lasting response with an immunecheckpoint inhibitor in a patient with SNUC.…”