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

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.

Artificial intelligence‐powered spatial analysis of tumor‐infiltrating lymphocytes as a predictive biomarker for axitinib in adenoid cystic carcinoma

“…Our data are consistent with those of previous studies that showed that ACC is a cancer with low immunogenicity, using immunohistochemistry 21–23 . It has been reported that immune checkpoint inhibitors are not effective in ACC, which may be in part a result of low immunogenicity 24,25 .…”

“…The level of TIL expression is not suitable as a predictive biomarker for immunotherapy in ACC, possibly due to a similar cause 22 . In a previous study analyzing TIL patterns in ACC, it was reported that the IP, represented by the spatial distribution of TIL, has no clear association with clinical outcomes 23 . Our analysis found that the IP in ACC was not associated with PFS with axitinib use.…”

“…22 In a previous study analyzing TIL patterns in ACC, it was reported that the IP, represented by the spatial distribution of TIL, has no clear association with clinical outcomes. 23 Our analysis found that the IP in ACC was not associated with PFS with axitinib use. This may be because the existing classification of IP is not suitable for ACC since the TIL infiltration of the cancer area of ACC is generally low, and there is little difference between them.…”

“…Our data are consistent with those of previous studies that showed that ACC is a cancer with low immunogenicity, using immunohistochemistry. [21][22][23] It has been reported that immune checkpoint inhibitors are not effective in ACC, which may be in part a result of low immunogenicity. 24,25 The level of TIL expression is not suitable as a predictive biomarker for immunotherapy in ACC, possibly due to a similar cause.…”

NKT cells contribute to alleviating lung metastasis in adenoid cystic carcinoma

“…It is considered an immunologically cold tumor characterized by a low tumor mutation burden, low expression of tumor antigens, and a microenvironment with limited immunity. [6][7][8][9] The details of the immunological processes underlying this phenomenon need further investigation.…”