Expression of Programmed Cell Death Ligand 1 and Associated Lymphocyte Infiltration in Olfactory Neuroblastoma

London, Nyall R.; Rooper, Lisa M.; Bishop, Justin A.; Xu, Huimin; Bernhardt, Lydia J.; Ishii, Masaru; Hann, Christine L.; Taube, Janis M.; Izumchenko, Evgeny; Gaykalova, Daria A.; Gallia, Gary L.

doi:10.1016/j.wneu.2019.11.112

Cited by 25 publications

(27 citation statements)

References 32 publications

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“…This result suggests that SNSCCs are immunogenic tumors and is in agreement with the previously published studies on SNSCCs and HNSCCs reporting CD8 + TILs in 35-50% of cases [15][16][17][18][19][20][21]. In contrast, in ITACs and low-grade ONBs, two other tumor types of the sinonasal region, CD8 + TILs were much less frequent and were predominantly found in the stromal compartment [22,23,29].…”

Section: Discussionsupporting

confidence: 92%

“…These two factors are reflected in TMIT I (CD8 high /PD-L1 pos ), which we observed in 19% of the SNSCCs, very similar to the 23% found by Quan et al [20]. This proportion is lower than in highly immunogenic tumors such as melanomas, renal cell and bladder cancers, HNSCCs or lung squamous cell carcinomas (40-50% of the cases belong to TMIT I) [25], but still higher than in other sinonasal cancers such as ITACs and ONBs [22,23,29].…”

Section: Discussionsupporting

confidence: 84%

“…Classifying our series of SNSCCs according to the TMIT did not yield additional prognostic information; TMIT I (CD8 high ) presented worse survival compared to TMITs II and III (both CD8 low ). This result contrasts with reports on other sinonasal tumors, including SNSCCs, ITACs, ONBs [15,[21][22][23]29] and histologically similar HNSCCs [17][18][19]25]. In fact, a positive relation between high CD8 + TIL scores and favorable prognosis is found in the majority of cancer types such as ovarian [30], renal [31], lung [32] and pancreatic cancers [33], although a number of studies have found high CD8 + TIL scores related to worse survival [34][35][36].…”

Section: Discussioncontrasting

confidence: 67%

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Prognostic and Therapeutic Implications of Immune Classification by CD8+ Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma

García-Marín

Reda

Riobello

et al. 2021

IJMS

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Sinonasal squamous cell carcinoma (SNSCC) is an aggressive tumor predominantly arising in the maxillary sinus and nasal cavities. Advances in imaging, surgical and radiotherapeutic techniques have reduced complications and morbidity; however, the prognosis generally remains poor, with an overall 5-year survival rate of 30–50%. As immunotherapy may be a new therapeutic option, we analyzed CD8+ tumor-infiltrating lymphocytes (TILs) and the tumor microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) in a series of 57 SNSCCs. Using immunohistochemistry, tissue samples of 57 SNSCCs were analyzed for expression of CD8 on TILs and of PD-L1 on tumor cells. The results were correlated to the clinical and survival data. In total, 88% (50/57) of the tumors had intratumoral CD8+ TILs; 19% (11/57)—CD8high (>10%); and 39/57 (68%)—CD8low (1–10%). PD-L1 positivity (>5%) was observed in 46% (26/57) of the SNSCCs and significantly co-occurred with CD8+ TILs (p = 0.000). Using univariate analysis, high intratumoral CD8+ TILs and TMIT I (CD8high/PD-L1pos) correlated with a worse survival rate. These results indicate that SNSCCs are immunogenic tumors, similar to head and neck squamous cell carcinomas. Nineteen percent of the cases were both CD8high and PD-L1pos and this subgroup may benefit from therapy with immune checkpoint inhibitors.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 84%

Section: Discussioncontrasting

confidence: 67%

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Prognostic and Therapeutic Implications of Immune Classification by CD8+ Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma

García-Marín

Reda

Riobello

et al. 2021

IJMS

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“…Olfactory neuroblastoma (ONB) or esthesioneuroblastoma (ENB) is a rare malignancy of the nasal cavity that likely arises from the olfactory neuro‐epithelium 1 . An olfactory epithelial origin is suggested by the tumor anatomical location, morphological features, and characteristic gene expression patterns 2 .…”

Section: Introductionmentioning

confidence: 99%

“…Olfactory neuroblastoma (ONB) or esthesioneuroblastoma (ENB) is a rare malignancy of the nasal cavity that likely arises from the olfactory neuro‐epithelium. 1 An olfactory epithelial origin is suggested by the tumor anatomical location, morphological features, and characteristic gene expression patterns. 2 ONB was first described in 1924 and named “L'esthesioneuroepitheliome olfactif.” 3 Due to lack of information on its histological origin, additional names have since been used including olfactory neurocytoma and others.…”

Section: Introductionmentioning

confidence: 99%

The genomics and epigenetics of olfactory neuroblastoma: A systematic review

Kaur

Izumchenko

Blakaj

et al. 2021

Laryngoscope Investig Oto

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Background Olfactory neuroblastoma (ONB) or esthesioneuroblastoma (ENB) is a rare malignancy of the nasal cavity believed to arise from the olfactory epithelium. The goal of this study was to systematically review the genomics, epigenetics, and cytogenetics of ONB and to understand the potential clinical implications of these studies. Methods A systematic literature review was performed for articles published before May 2020 using Cochrane, Embase, Pubmed, and Scopus databases. Inclusion criteria included genomics, cytogenetics, and epigenetics studies on ONB. Exclusion criteria included studies not in English or systematic reviews. Articles and abstracts were reviewed by two independent reviewers to reduce bias during article selection and synthesis of results. Of the 36 studies included in this review, 24 were research articles and 12 were abstracts. Results Although recurrent mutations among ONB tumors are uncommon, alterations in TP53, DMD, PIK3CA, NF1, CDKN2A, CDKN2C, CTNNB1, EGFR, APC, cKIT, cMET, PDGFRA, CDH1, FH, SMAD4, FGFR3 and IDH2 genes have been reported in several recent studies. In addition, cytogenetic studies revealed that the landscape of chromosomal aberrations varies widely amongst ONB tumors. Conclusions The rare character of ONB has limited the sample size available for cytogenetic, genomic, and epigenetic studies and contributes to the limitations of this systematic review. Comprehensive genomic and epigenomic studies with larger cohorts are warranted to validate the initial reports summarized in this review and to identify potential therapeutic targets for ONB.

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Long‐term oncologic outcomes in esthesioneuroblastoma: An institutional experience of 143 patients

McMillan

Gompel

Link

et al. 2022

Int Forum Allergy Rhinol

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Objective Esthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epithelium of the cribriform plate. The goal of this study was to update our oncologic outcomes for this disease and explore prognostic factors associated with survival. Materials and methods We performed a retrospective analysis of patients with ENB treated at a single tertiary care institution from January 1, 1960, to January 1, 2020. Univariate and multivariate analysis was performed. Overall survival (OS), progression‐free survival (PFS), and distant metastasis–free survival (DMFS) were reported. Results Among 143 included patients, the 5‐year OS was 82.3% and the 5‐year PFS was 51.6%; 5‐year OS and PFS have improved in the modern era (2005–present). Delayed regional nodal metastasis was the most common site of recurrence in 22% of patients (median, 57 months). On univariate analysis, modified Kadish staging (mKadish) had a negative effect on OS, PFS, and DMFS (p < 0.05). Higher Hyams grade had a negative effect on PFS and DMFS (p < 0.05). Positive margin status had a negative effect on PFS (p < 0.05). Orbital invasion demonstrated worsening OS (hazard ratio, 3.1; p < 0.05). On multivariable analysis, high Hyams grade (3 or 4), high mKadish stage (C+D), and increasing age were independent negative prognostic factors for OS (p < 0.05). High Hyams grade (3+4), high mKadish stage (C+D), age, and positive margin status were independent negative prognostic factors for PFS (p < 0.05). High Hyams grade (3+4) was an independent negative prognostic factor for DMFS (p < 0.05). Conclusions Patients with low Hyams grade and mKadish stage have favorable 5‐year OS, PFS, and DMFS.

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Expression of Programmed Cell Death Ligand 1 and Associated Lymphocyte Infiltration in Olfactory Neuroblastoma

Cited by 25 publications

References 32 publications

Prognostic and Therapeutic Implications of Immune Classification by CD8+ Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma

Prognostic and Therapeutic Implications of Immune Classification by CD8+ Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma

The genomics and epigenetics of olfactory neuroblastoma: A systematic review

Long‐term oncologic outcomes in esthesioneuroblastoma: An institutional experience of 143 patients

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