PD-L1 and PD-L2 Expression Levels Are Low in Primary and Secondary Adenoid Cystic Carcinomas of the Orbit: Therapeutic Implications

Wolkow, Natalie; Afrogheh, Amir; Kidd, Martin; Eagle, Ralph C.; Pai, Sara I.; Faquin, William C.

doi:10.1097/iop.0000000000001585

Cited by 14 publications

(9 citation statements)

References 37 publications

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“…Our data are consistent with previous studies that suggest that ACC tumours are associated with low immunogenicity and with minimal/absent PD-L1 expression in tumour cells [8][9]. However, in contrast to results published by Sridharan et al, we did not find PD-L1 expression in TILs, which may be attributed to the use of different antibody clones.…”

Section: Discussionsupporting

confidence: 90%

“…A study by Mosconi et al showed low intra-tumoural CD8+ TILs and absent PD-L1 expression in ACC tumours [8]. Similarly, a recent study by Wolkow et al showed low PD-L1 and PD-L2 expression, as well as sparse tumour infiltrating lymphocytes, in 23 cases of adenoid cystic carcinoma of the orbit [9]. In the current study, we aimed to further characterize the immune microenvironment of ACC tumours and evaluate survival outcomes based on TIL and PD-L1 expression.…”

Section: Introductionmentioning

confidence: 91%

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Assessment Of Tumour Infiltrating Lymphocytes And Pd-l1 Expression In Adenoid Cystic Carcinoma Of The Salivary Gland

Chen

Fung

McIntyre

et al. 2021

CIM

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Purpose: Early phase clinical studies are ongoing to evaluate the role of immune checkpoint inhibitors in adenoid cystic carcinoma (ACC) despite a paucity of information on the immune microenvironment. This study aims to better characterize the immune microenvironment of ACC tumours and evaluate survival outcomes based on tumour infiltrating lymphocyte (TIL) and programmed death-ligand 1 (PD-L1) expression. Methods: Patient characteristics, treatment and outcome data were collected for 24 ACC patients. The CD8+(cluster of differentiation 8) TIL and PD-L1 expression were quantified by immunohistochemistry. Marker expression and survival outcomes were evaluated by Kaplan-Meier analysis. Results: All cases were negative for PD-L1 expression; four cases had focal high, eight cases had focal moderate and 12 cases had low TIL expression. Based on TIL expression, there was no difference in disease-free or overall survival. Conclusion: Adenoid cystic carcinoma tumours were found to be associated with a poor immunogenic microenvironment, with absent PD-L1 expression and low CD8+ TILs. There was no association between TIL expression and survival. These data suggest that PD-L1 and TIL expression are unlikely to be useful as predictive biomarkers for response to immunotherapy.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 91%

Assessment Of Tumour Infiltrating Lymphocytes And Pd-l1 Expression In Adenoid Cystic Carcinoma Of The Salivary Gland

Chen

Fung

McIntyre

et al. 2021

CIM

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“…Thus, novel agents are urgently needed for advanced ACC. Immune checkpoint inhibitors have demonstrated antitumor activity in other malignancies of head and neck, but their impact in metastatic ACC seems to be limited due to the immune-excluded microenvironment of ACC (36)(37)(38). Researches focusing on the genomic landscape of ACC have identified several biomarkers including MYB, c-KIT, FGFR2, VEGFR, and Notch 1, which provided potential therapeutic targets for ACC (39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of anlotinib in metastatic adenoid cystic carcinoma: a retrospective study

Su¹,

Yu²,

Wang³

et al. 2022

Transl Cancer Res TCR

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Background: Metastatic adenoid cystic carcinoma (ACC) is a malignant tumor lacking effective therapies.We evaluated a multitargeted tyrosine kinase inhibitor anlotinib in patients with metastatic ACC.Methods: From September 2018 to October 2020, nineteen patients with histologically confirmed metastatic ACC of any primary site were treated with anlotinib 12 mg orally per day at the two-week on/ one-week off schedule at a single institution. Disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were analyzed. Adverse events (AEs) were recorded. Results:The DCR of anlotinib in metastatic ACC was 63.2% (12/19), including 1 partial response and 11 stable disease. After a median follow-up of 11.0 months, median PFS was 10.1 (95% CI: 6.8-14.8) months.Median OS was not reached. The most common AEs included hypertension (n=6, 32%), oral pain (n=6, 32%), hypothyroidism (n=6, 32%), hand-foot skin syndrome (n=5, 26%), proteinuria (n=5, 26%), fatigue (n=4, 21%), and anorexia (n=4, 21%). Grade 3 AEs occurred in two cases (oral pain and hand-foot skin syndrome) and could be managed.Conclusions: Anlotinib demonstrated antitumor activity and manageable toxicity in metastatic ACC patients. Thus, metastatic ACC patients could benefit from anlotinib as a palliative targeting therapy.

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“…Anecdotal evidence from case reports suggests that immune checkpoint inhibitors may have some benefit in lacrimal gland tumors [ 19 , 20 ]. However, concrete data from large-scale analyses are not available [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Current Trends in the Management of Epithelial Lacrimal Gland Tumors: A Retrospective National Cancer Database Analysis

Kumar¹,

Wang²,

Huang³

et al. 2022

Cureus

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Background: Lacrimal gland tumors are rare with data limited to very few large studies. Contemporary strategies like orbit sparing surgeries and neoadjuvant intraarterial chemotherapy remain controversial.Methods: This is a retrospective cohort analysis of epithelial lacrimal gland tumors from the 2004-2016 National Cancer Database. Patients were stratified based on the type of surgery (limited vs destructive) and various treatment modalities employed.Results: Squamous cell carcinoma (33.48%) and adenoid cystic carcinoma (29.45%) were the commonest histologies (N=669). Comparison of limited (46.33%) vs destructive procedures (53.11%) among 482 patients did not show any survival difference, nor the comparison between surgery vs ± chemotherapy vs ± radiotherapy among 472 patients.Conclusion: Squamous cell carcinoma and adenoid cystic carcinoma are the commonest types of lacrimal gland tumors seen in our study. Tumor spread from adjacent sites may have contributed to the higher percentage of squamous cell carcinomas seen. The type of surgery or chemoradiation use did not alter survival.

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PD-L1 and PD-L2 Expression Levels Are Low in Primary and Secondary Adenoid Cystic Carcinomas of the Orbit: Therapeutic Implications

Cited by 14 publications

References 37 publications

Assessment Of Tumour Infiltrating Lymphocytes And Pd-l1 Expression In Adenoid Cystic Carcinoma Of The Salivary Gland

Assessment Of Tumour Infiltrating Lymphocytes And Pd-l1 Expression In Adenoid Cystic Carcinoma Of The Salivary Gland

Efficacy and safety of anlotinib in metastatic adenoid cystic carcinoma: a retrospective study

Current Trends in the Management of Epithelial Lacrimal Gland Tumors: A Retrospective National Cancer Database Analysis

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