Current landscape and future directions of therapeutic approaches for adenoid cystic carcinoma of the salivary glands (Review)

Oncology Letters, Год журнала: 2025, Номер 29(3)

Опубликована: Янв. 22, 2025

Adenoid cystic carcinoma (ACC) of the salivary glands is second most common type gland cancer, and characterized by a poor prognosis an unclear pathology. The incidence ACC rare, as it accounts for 10-15% all tumors affects mainly patients aged between 50 60 years. annual rate estimated to be ~4.5 cases per 100,000 individuals. Due its rarity use contaminated cell lines in previous investigations, precise etiological factors underlying remain poorly understood. Current treatment modalities, typically involving surgery with or without postoperative radiotherapy, often prove unsatisfactory due potential local recurrence delayed distant metastases, which may manifest 3-5 years after constitute primary failure existing therapeutic approaches. indolent growth pattern, along perineural perivascular invasion, potentially responsible onset metastases. No effective systemic therapy has been established so far. Therefore, management represents significant challenge. Exploring molecular characteristics ACC, including reasons behind propensity invasion correlation immune system, offers promising strategies managing could open up novel pathways future interventions. Currently, immunotherapy shown limited effectiveness. While exact mechanism lack response remains unknown, low levels tumor-infiltrating lymphocytes these contribute this resistance. identifying targets enhance against tumor cells essential. present review provides update on clinical studies explores that ACC.

Язык: Английский

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Exploring Immunological Effects and Novel Immune Adjuvants in Immunotherapy for Salivary Gland Cancers

Cancers, Год журнала: 2024, Номер 16(6), С. 1205 - 1205

Опубликована: Март 19, 2024

Salivary gland cancer (SGC) is rare and comprises over 20 histological subtypes. Recently, clinical experience regarding immunotherapies for SGCs has been accumulating, yet their efficacy remains controversial. Understanding the tumor microenvironment (TME), including expression of immune checkpoint molecules in SGC, crucial to optimizing immunotherapy. In this review, we demonstrate that high-grade mucoepidermoid carcinoma salivary duct generally exhibit immune-hot TME with high cell infiltration, frequent genetic mutations, robust molecule expression. contrast, adenoid cystic carcinomas an immune-cold TME. While reported inhibitors (ICIs) poor, several studies showed promising ICIs, objective response rate ranging from 20.0–33.3%, indicating ICIs might be beneficial a specific population SGC. Molecule-targeted therapies anti-human epidermal growth factor receptor 2 anti-androgen have shown against Recent evidence indicates these could targets antigen-specific chimeric antigen receptor-T therapy vaccines. This review discusses current understanding future directions SGCs, ongoing trials.

Язык: Английский

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Cancer neuroscience in head and neck: interactions, modulation, and therapeutic strategies

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Март 31, 2025

Head and neck cancer (HNC) is an aggressive malignancy with significant effects on the innervation. Not only it at top of spectrum a dismal prognosis, but also imposes considerable stress patients society owing to frequent neurological symptoms. With progress in neuroscience, interactions between HNC nervous system, as well underlying mechanisms, have become increasingly clear. Compelling evidence suggests communication information nerve cells devastation system tumor growth. However, thorough grasp neuroscience has been severely constrained by intricacy fragmented research. This review comprehensively organizes summarizes latest research crosstalk system. It aims clarify various aspects HNC, including physiology, progression, treatment cancer. Furthermore, opportunities challenges are discussed, which offers fresh perspectives diagnosis management.

Язык: Английский

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Tumor immune microenvironment in adenoid cystic carcinoma of the lacrimal gland: relationship with histopathology and prognosis

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Март 31, 2025

To quantitatively investigate the pathological subtypes of lacrimal gland adenoid cystic carcinoma (LGACCs), tumor immune microenvironment in each subtype, and relation to survival. In this retrospective study, subtype was determined by H&E staining. Multiplex immunochemistry performed define specific cells. The (TIME) sketched sequential image scanning reconstructed a cytometry platform. Eighteen patients with adequate paraffin blocks diagnosed LGACC from 2012 2021 were included study. Thirteen out eighteen (72.2%)showed mixture different subtypes. Each took percentages on tumors. cribriform most common taking an overall percentage 39%. rest tubular (19%), basaloid (17%), (C + T) 14%. sclerosing comedocarcinomic least seen LGACC, 11% altogether. Patients dominant component had better survival than non-cribriform patients. worse clinical outcomes non-basaloid ones. TIME showed high immunogenicity margin but declined areas. Pathological rather individual differences phenotype. possessed more cell infiltration other is composed multiple takes tumors, which related prognosis. pattern varies among subtypes, could indicate novel strategies immunotherapy.

Язык: Английский

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Reversible downregulation of HLA class I in adenoid cystic carcinoma

Journal for ImmunoTherapy of Cancer, Год журнала: 2025, Номер 13(4), С. e011380 - e011380

Опубликована: Апрель 1, 2025

Background Adenoid cystic carcinoma (ACC) is a rare, but lethal cancer with low response rates to systemic therapies, such as cytotoxic chemotherapy and immune-checkpoint inhibitors (ICIs). Despite extensive clinical trials, no effective treatments for patients recurrent or metastatic ACC are available, mortality remain poor. Methods We employed automated multiplex immunofluorescence (mIF), single-cell RNA sequencing (scRNA-seq) Gene Expression analysis, in-situ hybridization, spatial transcriptomics analysis characterize the immune landscape of tumors, metastasis, normal tissues from regions where ACCs arise. Based on results these studies, we treated freshly resected interferon-γ stimulator interferon genes (STING) agonist in vitro. Additionally, included one patient phase 1 study novel STING (dazostinag) plus pembrolizumab. Results The mIF revealed that tumors immunologically “cold”, few tumor-infiltrating T-lymphocytes programmed death-ligand (PD-L1) expression. most striking finding was very beta-2-microglobulin (B2M) expression nearly all ACCs, only focal found some metastases. analyses salivary gland breast p63+, NFIB+, basal duct cell population, similarly B2M/human leukocyte antigen (HLA) class I Spatial focally B2M-positive metastases uncovered genetic pathway driving upregulation B2M, an program mediating reintroduction HLA-I/B2M; significantly upregulated IRF1, GBP1, TAP1 . On short-term treatment primary vitro agonist, observed strongly HLA I/B2M Moreover, recurrent, pembrolizumab led partial 70% tumor reduction. Conclusions Low B2M/HLA may explain why cold lack ICIs. Our findings suggest origin exists B2M/HLA-class state, pharmacologic manipulation activators, agonists, can restore HLA/B2M supported by promising ACC. These indicate potential path urgently needed immunotherapies.

Язык: Английский

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Stroma‐and Tumor‐Associated Predictive Features in Salivary Gland Adenoid Cystic Carcinoma of the Head and Neck

Journal of Oral Pathology and Medicine, Год журнала: 2024, Номер 54(1), С. 22 - 30

Опубликована: Ноя. 10, 2024

ABSTRACT Background There is lack of knowledge on the utility prognostic histopathologic characteristics in adenoid cystic carcinoma (ACC) head and neck. We evaluated value tumor stroma‐related features ACC. Materials Methods A total 65 cases ACC from minor major salivary glands were included this study. budding, tumor‐infiltrating lymphocytes (TILs), tumor‐stroma ratio (TSR) hematoxylin eosin (HE) stained sections. Results Stroma‐rich ACCs recurred more frequently ( p = 0.029) during follow‐up associated with distant metastasis 0.038). In multivariable analysis, stroma‐rich tumors poorer disease‐specific survival a hazard 3.76 (95% CI 1.10–12.83, 0.034). commonly showed low infiltration TILs as 89% was characterized by an immune desert pattern. Low significantly increased budding 0.039). Conclusion Adverse TSR are widely expressed ACC, poor prognosis. number tissue indicates weak response host illustrates nature relentless malignancy.

Язык: Английский

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Immunohistochemical Assessment of the Role of Tumor Microenviroment Associated with Odontogenic Neoplasms

Advanced Dental Journal, Год журнала: 2024, Номер 6(3), С. 511 - 521

Опубликована: Июль 1, 2024

Background: The diverse clinical behavior of the odontogenic neoplasms remains indistinct and may be related to surrounding microenvironment these neoplasms. immunohistochemical expression CD163 CD34 as elements tumor were evaluated in different variable nature correlate them with behavior.15 cases benign tumors, 15 locally aggressive malignant investigated by immunohistochemistry. count number macrophages blood capillaries stroma cells was detected each section study groups. Results: Statistical analysis revealed a statistically significant difference between studied groups regarding expressing benign, aggressive, A positive correlation Pearson Correlation test both stains behavior. Conclusions: link is observed increase M2 (expressing CD163) microvessel density CD34) cells; are strongly aggressiveness nature.

Язык: Английский

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Reversible Downregulation of HLA Class I in Adenoid Cystic Carcinoma

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 7, 2024

Abstract Purpose Adenoid cystic carcinoma (ACC), a rare and lethal cancer, has shown low response rates to systemic therapies, such as cytotoxic chemotherapy immune-checkpoint inhibitors (ICIs). Despite numerous clinical trials, some employing aggressive ICI combinations, no effective treatments for patients with recurrent or metastatic adenoid have emerged, ACC mortality remain stagnant. Therefore, we aimed characterize the immune landscape understand poor ICIs. Experimental Design We leveraged automated multiplex immunofluorescence (mIF), RNA in-situ hybridization, scRNAseq Gene Expression analysis identify pathways supporting cold environment molecularly tumors, adjacent normal tissues, tissues from regions where ACCs arise. In vitro, treated freshly resected interferon-ψ STING agonist. Results mIF demonstrated that tumors are immunologically ‘cold’, few tumor- infiltrating T-lymphocytes (TILs) PD-L1 expression. The most striking finding, however, was very HLA/B2M class I expression in almost all ACCs, which reversible through treatment RNAseq analyses of revealed p63+, NFIB+, basal duct cell population similarly Conclusions Low/absent may explain tumors’ status lack Our findings suggest origin exists an HLA-low state, pharmacologic manipulation activators, agonists, can restore creating path urgently needed, immunotherapies.

Язык: Английский

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Tumor Immune Microenvironment in Adenoid Cystic Carcinoma of the Lacrimal Gland: Relationship with Histopathology and Prognosis

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 8, 2024

Purpose: To quantitatively investigate the pathological subtypes of lacrimal gland adenoid cystic carcinoma (LGACCs), tumor immune microenvironment in each subtype, and relation to survival. Methods: In this retrospective study, subtype was determined by H&E staining. Multiplex immunochemistry performed define specific cells. The (TIME) sketched sequential image scanning reconstructed a cytometry platform. Results: Thirteen patients LGACCs showed mixture different with varied percentages. cribriform most common taking an overall percentage 39%. rest were tubular (19%), basaloid (17%), (C+T) 14%. sclerosing comedocarcinomic least seen LGACC, 11% altogether. Patients dominant component had better survival than non-cribriform patients. worse clinical outcomes non-basaloid ones. TIME high immunogenicity margin but declined areas. Pathological rather individual differences phenotype. possessed more cell infiltration other subtypes. Conclusions: LGACC is composed multiple percentages, which related prognosis. pattern among subtypes, could indicate novel strategies immunotherapy.

Язык: Английский

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