Patterns of Tumor Infiltrating Lymphocytes in Adenoid Cystic Carcinoma of the Head and Neck

SIMPLE SUMMARY: Adenoid cystic carcinoma (ACC) is a rare tumor with late occurring metastases and recurrences, which makes it necessary for patients to be monitored closely even beyond the usual five years. So far, there is hardly any effective treatment in the palliative situation and trials on immunotherapeutic drugs have not been successful. We sought to find possible prognostic markers by analyzing patterns of tumor infiltrating immune cells and additionally to learn more about possible reasons for this lack of response to immunotherapy. It appears from our data that it is not relevant for prognosis if the tumor is infiltrated by immune cells. This might also be the reason that immunotherapies do not work in this particular disease, which suggests that ACC is not recognized by infiltrating immune cells. Therefore, the tumor would have to be made visible to the immune system, for example, through vaccinations. ABSTRACT: Adenoid cystic carcinoma (ACC) is a rare malignancy in the head and neck. The prognosis remains poor and late recurrences often occur after 5 years and later. To date, there are no reliable prognostic markers for ACC. In several solid tumors, tertiary lymphoid structures (TLS) are associated with improved survival. This study aims to investigate the role of distribution patterns of tumor infiltrating immune cells (TIL) in ACC. A cohort of 50 patients from three different cancer centers was available for analysis. Sections were stained for CD3, CD4, CD8 and CD20 and evaluated with regard to their distribution of TIL. Patterns were determined as infiltrated-excluded, infiltrated-inflamed and presence of tertiary lymphoid structures. About half of the cases showed an infiltrated-excluded TIL pattern and only a minority of six cases had TLS present within the tumor. Within the inflamed phenotype CD3+ cells were by far the most abundant lymphocyte subtype, and within this compartment, CD8+ T cells were predominant. There was no influence on overall or disease-free survival by any of the TIL patterns. This indicates that ACC is a tumor with very low immunogenicity and even abundance of lymphocytes does not seem to improve prognosis for this disease. Therefore, the observed lack of response towards immunotherapy is not surprising and other methods to induce recognition of ACC by the immune system must be found.