Immunologic “Cold” Squamous Cell Carcinomas of the Head and Neck Are Associated With an Unfavorable Prognosis

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) represents a common cancer worldwide. Past therapeutic advances have not significantly improved HNSCC prognosis. Therefore, it is necessary to further stratify HNSCC, especially with recent advances in tumor immunology.Methods: Tissue microarrays were assembled from tumor tissue samples and were complemented with comprehensive clinicopathological data of n = 419 patients. H&E whole slides from resection specimen (n = 289) were categorized according to their immune cell infiltrate as “hot,” “cold,” or “excluded.”Results: Investigating tumor immune cell patterns, we found significant differences in survival rates. Immunologic “hot” and “excluded” HNSCCs are associated with better overall survival than “cold” HNSCC patients (p < 0.05). Interestingly, the percentage of all three patterns is nearly identical in p16 positive and negative HNSCCs.Conclusions: Using a plain histological H&E approach to categorize HNSCC as being immunologic “hot,” “cold,” or “excluded” can offer a forecast of patients' prognosis and may thus aid as a potential prognostic tool in routine pathology reports. This “hot-cold-excluded” scheme needs to be applied to more HNSCC cohorts and possibly to other cancer types to determine prognostic meaning, e.g., regarding OS or DFS. Furthermore, our cohort reflects epidemiological data in the national, European, and international context. It may, therefore, be of use for future HNSCC characterization.

Spatial Distribution of Immune Cells in Head and Neck Squamous Cell Carcinomas

“…With the limited number of patients, we cannot provide any prognostic value of the TGF-b expression. But as we described worse OS for cold tumors in our previous study (28) and as all of these tumors were not treated with ICIs, we do not expect a prognostic value of TGF-b expression for the established standard therapy regimens of HNSCC. However, we are keen to learn about TGF-b analyses in future cohorts receiving ICI treatments.…”

“…This was independent of other known risk classifications such as the T stage, UICC stage, p16 expression, grading, sex, and age. Interestingly, there was no difference between p16-positive and p16-negative cancers in relation to excluded, cold, and hot cases, with 52.8% excluded, 24.8% cold, and 22.4% hot HNSCC in the p16-negative group versus 53.5% excluded, 23,9% cold, and 22.5% hot HNSCC in the p16-positive group (28). In the present study, we wanted to provide initial insights into the distribution of the different immune cell types in hot, cold, and excluded HNSCC.…”

“…We established an HNSCC cohort as previously described by obtaining archived tissue samples (28). The cohort contained hot, cold, and excluded tumor tissues.…”

Performance of Different Diagnostic PD-L1 Clones in Head and Neck Squamous Cell Carcinoma

“…As described previously, our cohort is well-representative for HNSCCs and well-reflects the aggressive tumor behavior (19). Briefly, our cohort mirrors the typical characteristics for HNSCC patients: three-quarters were men with smoking and alcohol as common nutritive-toxic pathogens.…”

“…Tissue samples were routinely fixated in 4% buffered neutral formalin for 12-24 h. After paraffin embedding the preserved tissue blocks were stored at room temperature in our archives until they were retrieved. We accessed our large and comprehensively clinicopathologically characterized HNSCC cohort, as described before (19,20). For the study at hand, we selected those TMAs from our cohort that contained tumor tissue of recurrent disease and matching primary tumors (n = 75 patients).…”