Immune microenvironment and evasion mechanisms in adenoid cystic carcinomas of salivary glands

Mosconi, Carla; Arruda, José Alcides Almeida de; Farias, Ana Caroline Rodrigues De; Oliveira, Gabriella Alves Quixabeira; Paula, Henrique Moura de; Fonseca, Felipe Paiva; Mesquita, Ricardo Alves; Silva, Tarcı́lia Aparecida; Mendonça, Elismauro Francisco; Batista, Aline Carvalho

doi:10.1016/j.oraloncology.2018.11.028

Cited by 69 publications

(82 citation statements)

References 32 publications

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“…Checkpoint inhibitor monotherapy is unlikely to achieve high response rates in any of these cancers. CD83+ cell populations 46 , in agreement with our observation that 80% of the ACCs in our study were in the immune-poor cluster, likely driven by a T cell exclusion phenotype.…”

Section: Discussionsupporting

confidence: 92%

“…It is important to clarify that in view of the small number of tumors analyzed, these findings are hypothesis-generating. However, a similar association between T cell infiltration and tumor recurrence was recently observed in ACC by Mosconi and colleagues 46 . In our study, this association was not observed in SDCs, perhaps because there were very few SDCs as immune-depleted as the ACCs and MECAs.…”

Section: Immune Infiltration Correlates With Aggressive Clinical Behasupporting

confidence: 78%

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The Immune Microenvironment and Neoantigen Landscape of Aggressive Salivary Gland Carcinomas Differ by Subtype

Linxweiler

Kuo

Katabi

et al. 2020

Clinical Cancer Research

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In this study, we characterize the immune microenvironment and neoantigen landscape of salivary gland cancers using RNA sequencing in 76 tumors representing the 3 most lethal histologies: adenoid cystic carcinoma (ACC), myoepithelial carcinoma (MECA), and salivary duct carcinoma (SDC). We show that SDCs exhibited high levels of immune infiltration, with corresponding higher levels of T cell dysfunction, and higher mutational load. ACCs were characterized by an immuneexcluded microenvironment, the presence of M2-polarized macrophages and myeloidderived suppressor cells, and very low mutational load. MECAs were more heterogeneous, with both immune-low and immune-high phenotypes. Across all SGCs, immune infiltration was associated with mutation-and fusion-derived neoantigens. These findings provide new insights into the immune microenvironment and neoantigen landscape of SGCs, showing that mechanisms of immune escape differ by histology. These data nominate potential immunologic vulnerabilities and may help guide the next steps of investigation in precision immunotherapy for these difficult-to-treat cancers. Research.

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Section: Discussionsupporting

confidence: 92%

Section: Immune Infiltration Correlates With Aggressive Clinical Behasupporting

confidence: 78%

The Immune Microenvironment and Neoantigen Landscape of Aggressive Salivary Gland Carcinomas Differ by Subtype

Linxweiler

Kuo

Katabi

et al. 2020

Clinical Cancer Research

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show abstract

“…Our results highlighted that ACC tumors have the lowest median APM score and immune infiltration median (Figures 3A, B). The expression of APM genes and IFN- (65,66), which was associated with b-catenin/Wnt and PI3K pathways (67,68). Moreover, immune tolerance phenotype tumors are also accompanied by low or no PD-L1 expression (69), as observed in our ACC cohort.…”

Section: Discussionsupporting

confidence: 66%

The Immune Landscape of Chinese Head and Neck Adenoid Cystic Carcinoma and Clinical Implication

Dou

He³

et al. 2021

Front. Immunol.

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Novel systemic agents and effective treatment strategies for recurrence adenoid cystic carcinoma (ACC) of the head and neck are still worthy of further exploration. Here, we analyzed the mutations and expression profiles of 75 Chinese ACC patients, characterized the prognostic value of the immune signature for recurrence or distant metastasis, and explored the potential of immunotherapeutic biomarkers in ACC. In general, MYB fusion and somatic mutations accounted for a high proportion, which was 46.7% (35/75). ACCs displayed an overall low mutation burden and lack of programmed cell death ligand-1 (PD-L1) expression. The antigen-presenting machinery (APM) expression score and immune infiltration score (IIS) were the lowest among ACC patients, compared with other cancer types. For 61 primary cases, the locoregional recurrence-free survival (LRRFS) was statistically significantly correlated with the IIS [univariate analysis; hazard ratio (HR) = 0.32; 95% CI, 0.11–0.92; p = 0.035] and T-cell infiltration score (TIS) (univariate analysis; HR = 0.33; 95% CI, 0.12–0.94; p = 0.037]. Patients with lower IIS (log-rank p = 0.0079) or TIS (log-rank p = 0.0079) had shorter LRRFS. Additionally, solid pattern was also a prognostic factor related to locoregional recurrence, whereas postoperative radiotherapy (PORT) exerted its beneficial effects. We further evaluated the pretreatment immune profile of five ACC patients treated with PD-1 inhibitors. Patients who responded to camrelizumab or pembrolizumab observed elevated APM and TIS, compared with patients with progressive disease. Our study highlights the immune infiltration pattern and messenger RNA (mRNA) signatures of Chinese ACC patients, which has the potential value for prognosis and immunotherapy.

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“…Chang et al reported that CD8 + TILs were significant predictive factors of relapse‐free survival according to univariate analysis but not multivariate analyses 27 . In addition, Mosconi et al also reported that CD8 + TIL density in the stromal and intratumor regions was associated with tumor recurrence in SGC patients with adenoid cystic carcinoma, and higher CD8 + TIL density in the stroma resulted in a favorable prognosis 28 . However, in the present study, there was no significant difference between CD8 + TIL density and DFS or OS.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Tumor Proportion Score in Salivary Gland Carcinoma

et al. 2020

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Objective Limited information is available regarding the role of programmed death ligand 1 (PD‐L1) expression and CD8+ tumor‐infiltrating lymphocyte (TIL) density in the tumor immune microenvironment (TIM) of patients with salivary gland carcinoma (SGC). This study aimed to assess the association between the prognosis of SGC patients and the probability of PD‐L1 expression in tumor and/or immune cells using the tumor proportion score (TPS), mononuclear immune cell density score (MIDS), combined positive score (CPS), and CD8+TIL density in the TIM. Study Design Retrospective cohort study. Methods We retrospectively reviewed 73 SGC patients treated with definitive surgery between 2000 and 2015. Immunohistochemical analysis was used to assess TPS, MIDS, CPS, and CD8+TIL density, followed by prognostic evaluation of these immune‐related parameters. Results Histological grade was associated with TPS, MIDS, and CPS based on PD‐L1 expression, and these scores exhibited a significant association with CD8+TIL density. Patients with positive TPS had an unfavorable disease‐free survival and overall survival. Multivariate analyses indicated that the TPS was a significant and independent prognostic factor. Conclusion Our results suggest that TPS might be a useful prognostic biomarker in SGC patients receiving definitive surgery. Laryngoscope, 131:E1481–E1488, 2021

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Immune microenvironment and evasion mechanisms in adenoid cystic carcinomas of salivary glands

Cited by 69 publications

References 32 publications

The Immune Microenvironment and Neoantigen Landscape of Aggressive Salivary Gland Carcinomas Differ by Subtype

The Immune Microenvironment and Neoantigen Landscape of Aggressive Salivary Gland Carcinomas Differ by Subtype

The Immune Landscape of Chinese Head and Neck Adenoid Cystic Carcinoma and Clinical Implication

Prognostic Value of Tumor Proportion Score in Salivary Gland Carcinoma

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