Prognostic Value of Tumor-Infiltrating Lymphocytes in Sinonasal Mucosal Melanoma.

Tumor-infiltrating lymphocytes (TILs) predict better outcome in several types of cancers. However, the prognostic value of TILs in sinonasal mucosal melanoma (SNMM) is uncertain. Here, we investigated whether TILs can be used as a prognostic indicator for survival in SNMM. Retrospective cohort study. Patient history and histologic specimens from 27 patients with primary SNMM were retrospectively analyzed. TIL grade was determined and associations between TILs and AJCC tumor stage, overall survival, and recurrence-free survival were analyzed. Patients with TILs in the primary tumor classified as brisk or non-brisk survived significantly longer than patients with SNMMs lacking lymphocyte infiltrates. Brisk TILs were associated with the lower T3 stage and increased recurrence-free and 5-year survival. Our results indicate that TIL density is a strong prognostic factor for better survival in SNMM. Prospective studies with larger case numbers are warranted to determine whether TILs should be included in future AJCC staging guidelines. 3 Laryngoscope, 132:1334-1339, 2022.

Ledderose S ，Ledderose C ，Penkava J ，Ledderose GJ ... -  《-》

Characterization of the tumor-infiltrating lymphocyte landscape in sinonasal mucosal melanoma.

Tumor-infiltrating lymphocytes (TILs) are important prognostic biomarkers in several types of cancers. The interplay between TIL subgroups and immune checkpoint molecules like programmed cell death ligand 1 (PD-L1) is a promising target for immunotherapy. However, the TIL landscape in sinonasal mucosal melanoma (SNMM) has not been sufficiently characterized yet and the prognostic value of TIL subgroups and PD-L1 expression remains uncertain. Here, we investigated subsets of TILs (CD3+, CD4+, CD8+, CD20+) and PD-L1 expression patterns in SNMM and assessed their prognostic value for recurrence-free and overall survival. Immunohistochemical staining for CD3, CD4, CD8, CD20 and PD-L1 was performed on tumor tissue from 27 patients with primary SNMM. Patient history was obtained and associations between TIL subgroups or PD-L1 expression and AJCC tumor stage, overall survival, and recurrence-free survival were retrospectively analyzed. Patients with high CD3+ and CD8+ TILs in the primary tumor survived significantly longer than patients with SNMMs with a low number of CD3+ and CD8+ TILs. High CD3+ and high CD8+ TILs were associated with the lower T3 stage and increased 5-year survival. PD-L1 positivity in tumor cells was associated with advanced tumor stage. Our results indicate that high densities of CD3+ and CD8+ TILs are strong positive prognostic biomarkers for survival in SNMM. Prospective studies with larger case numbers are warranted to confirm our findings.

Ledderose S ，Schulz H ，Paul T ，Ledderose C ，Ledderose GJ ... -  《-》

Expression of immune checkpoint molecules TIGIT and TIM-3 by tumor-infiltrating lymphocytes predicts poor outcome in sinonasal mucosal melanoma.

Sinonasal mucosal melanoma (SNMM) is a rare but aggressive tumor with a poor prognosis. The co-inhibitory receptors T cell immunoglobulin and mucinodomain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3) and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) are promising new targets in anti-cancer immunotherapy. The expression profiles of these immune checkpoint molecules (ICMs) and potential prognostic implications have not been characterized in SNMM yet. Immunohistochemical staining for TIGIT, LAG-3 and TIM-3 was performed on tumor tissue samples from 27 patients with primary SNMM. Associations between ICM expression and demographic parameters, AJCC tumor stage, overall survival, and recurrence-free survival were retrospectively analyzed. SNMM patients with low numbers of TIGIT+ and TIM-3+ tumor infiltrating lymphocytes (TILs) in the primary tumor survived significantly longer than patients with a high degree of TIGIT+ and TIM-3+ TILs. High infiltration with TIM-3+ or TIGIT+ lymphocytes was associated with the higher T4 stage and decreased 5-year survival. We identified high densities of TIM-3+ and TIGIT+ TILs as strong negative prognostic biomarkers in SNMM. This suggests that TIM-3 and TIGIT contribute to immunosuppression in SNMM and provides a rationale for novel treatment strategies based on this next generation of immune checkpoint inhibitors. Prospective studies with larger case numbers are warranted to confirm our findings and their implications for immunotherapy.

Ledderose S ，Ledderose C ，Ledderose GJ 《-》

Sinonasal Mucosal Melanoma: Role of Tumor Proliferative Indices and Pathological Factors in Survival.

The objective of this study is to determine the association of proliferation indices and pathologic biomarkers on overall and recurrence/metastasis-free survival (OS and RMFS) in patients with sinonasal mucosal melanoma (SNMM) and to assess the genetic mutational landscape of SNMM. This is a retrospective cohort study of 45 SNMM patients without neoadjuvant therapy who underwent surgical therapy with curative intent and had tumor tissue available for histopathologic review, molecular analysis, and genetic mutational assessment. The OS and RMFS were assessed for associations with numerous tumor and patient-related factors. Among proliferative indices, higher Ki67 and mitotic rates were associated with worsened OS and RMFS (Ki67: p = 0.0007 and p < 0.0001; mitotic rate: p = 0.005 and p = 0.0009, respectively). The presence of brisk tumor-infiltrating lymphocytes (TILs) was associated with improved RMFS (p = 0.007) and the presence of lymphovascular invasion was associated with worsened OS and RMFS (p = 0.02 and p = 0.04, respectively). Patients with amelanotic tumors were more likely to have higher T-stage (p = 0.046), less likely to have brisk TILs (p = 0.02) and had worsened RMFS (p = 0.03). Patients on immunotherapy with tumor Ki67 < 40% had better 3-year OS compared to those with higher Ki67 index (p = 0.004). Actionable genetic mutations such as BRAF V600E are rare and present in only 1 of 20 patients tested. In SNMM patients, pathologic and proliferation markers such as Ki67, mitotic rate and brisk TILs are associated with survival and may be considered in future staging systems. Clinical response to immunotherapy appears to correlate with the Ki67 index. Given the distinct genetic profile of SNMM, targeted therapies against the MAPK kinase pathway have limited utility. 3 Laryngoscope, 132:2350-2358, 2022.

Guo R ，Jenkins SM ，Johnson BJ ，Reed K ，Kroneman T ，Choby G ... -  《-》

Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study.

Thomas NE ，Busam KJ ，From L ，Kricker A ，Armstrong BK ，Anton-Culver H ，Gruber SB ，Gallagher RP ，Zanetti R ，Rosso S ，Dwyer T ，Venn A ，Kanetsky PA ，Groben PA ，Hao H ，Orlow I ，Reiner AS ，Luo L ，Paine S ，Ollila DW ，Wilcox H ，Begg CB ，Berwick M ... -  《-》