Corrigendum: Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease

Villeneuve, Larissa Di; Souza, Ive Lima; Tolentino, Fernanda D'Avila Sampaio; Ferrarotto, Renata; Schvartsman, Gustavo

doi:10.3389/fonc.2021.669486

Cited by 3 publications

(1 citation statement)

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“…We tested the samples for the presence of MYB-NFIB or MYBL1-NFIB fusion to confirm the pathological distinction of ACC. Around 65% of ACC had a MYB-NFIB and 4% a MYBL1-NFIB fusion, in concordance with the reported proportions from literature 46 . None of the non-ACC samples had a MYB-NFIB fusion.…”

Section: Resultssupporting

confidence: 90%

Integrative analysis reveals a macrophage-predominant, immunosuppressive immune microenvironment and subtype-specific therapeutic vulnerabilities in advanced salivary gland cancer

Zuljan,

von der Emde,

Piwonski

et al. 2024

Preprint

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BackgroundSalivary gland cancers (SGC) are rare and heterogeneous malignant tumors. Advanced SGC lack established treatment options and show poor response to immunotherapy. Here, an integrative multi-omics analysis in a large cohort of advanced SGC revealed insights into the tumor immune microenvironment (TIM) and distinct mechanisms of immune evasion.MethodsA total of 104 patients with recurrent/metastatic SGC from the DKTK MASTER program were included in this study. Whole-exome or whole-genome sequencing and RNA-sequencing was performed on fresh frozen tumor tissue. The tumor immune microenvironment was analyzed using CIBERSORT deconvolution analysis and immune gene expression scores in bulk RNA-sequencing data. Single-nuclei sequencing and immunohistochemistry analyses were performed in selected samples. Results were validated in bulk RNA-sequencing data of a previously published independent dataset.ResultsBulk transcriptome analysis revealed an immune-deserted TIM in the majority of advanced SGC samples. Immune exclusion was most prominent in adenoid cystic carcinoma (ACC) subgroup 1 exhibiting a downregulation of the antigen processing machinery. Only a small subset of advanced SGC, including few adenoid cystic carcinoma, exhibited T-cell inflammation, which was correlated with tumor mutational burden in Non-ACC samples. Subtype specific expression of immune checkpoints as well as cancer testis antigens were identified with prominent expression of VTCN1 in luminal cells within ACC. Single-cell RNA-sequencing and bulk RNA-seq deconvolution analysis validated immune cell exclusion and revealed a TIM that was dominated by M2 macrophages across SGC subtypes. Among evaluable patients treated with immune checkpoint inhibitors, a high T-cell to macrophage ratio was associated with clinical benefit.ConclusionsThese data support biomarker-based development of immune-checkpoint inhibition and the development of novel immune-checkpoint inhibitors and cellular therapies in SGC.Trial RegistrationRetrospectively registered,NCT05852522

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Section: Resultssupporting

confidence: 90%