Immunoarchitectural Pattern and Its Potential Prognostic Value in Mucoepidermoid Carcinoma

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Abstract
Objectives: To define tumor immunoarchitectural patterns (IPs) and characterize the immune profile in salivary gland mucoepidermoid carcinoma (MEC) toward assessing MEC prognostic significance and implications for immunotherapy. Methods: This study analyzed 41 MEC cases, evaluating the tumor IPs and tumor‐infiltrating lymphocyte (TIL) parameters by using whole‐slide imaging and AI‐assisted assessment. Immunohistochemistry of CD3 and CD8 markers was performed to assess key lymphocyte subpopulations. Results: Immune‐rich (I‐rich) tumors were characterized by high TIL density and were associated with aggressive tumor behavior, particularly in histological high‐grade MEC, with a significant increase in TIL density observed in the inner invasive margin compartment ( p < 0.05). I‐rich tumor cases were linked to poorer disease‐free survival (DFS) (Breslow = 4.686, p = 0.03). Aggressive MEC cases displayed a highly heterogeneous TIL profile, however, no TIL patterns showed a significant impact on DFS ( p > 0.05). Conclusions: Despite the high immunogenicity suggested by the abundance of T lymphocytes, the protective role of CD8+ T lymphocytes was not prominent in MEC. I‐rich tumors appeared more aggressive and unfavorable MEC cases exhibited high heterogeneity in their TIL profiles. Interrogating the role of TILs in the inner invasive tumor margin may offer a new mechanistic understanding for future immunotherapy discovery.

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