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98


A membrane-associated MHC-I inhibitory axis for cancer immune evasion

Chen, Xufeng; Lu, Qiao; Zhou, Hua; Liu, Jia; Nadorp, Bettina; Lasry, Audrey; Sun, Zhengxi; Lai, Baoling; Rona, Gergely; Zhang, Jiangyan; Cammer, Michael; Wang, Kun; Al-Santli, Wafa; Ciantra, Zoe; Guo, Qianjin; You, Jia; Sengupta, Debrup; Boukhris, Ahmad; Zhang, Hongbing; Liu, Cheng; Cresswell, Peter; Dahia, Patricia L M; Pagano, Michele; Aifantis, Iannis; Wang, Jun
Immune-checkpoint blockade has revolutionized cancer treatment, but some cancers, such as acute myeloid leukemia (AML), do not respond or develop resistance. A potential mode of resistance is immune evasion of T cell immunity involving aberrant major histocompatibility complex class I (MHC-I) antigen presentation (AP). To map such mechanisms of resistance, we identified key MHC-I regulators using specific peptide-MHC-I-guided CRISPR-Cas9 screens in AML. The top-ranked negative regulators were surface protein sushi domain containing 6 (SUSD6), transmembrane protein 127 (TMEM127), and the E3 ubiquitin ligase WWP2. SUSD6 is abundantly expressed in AML and multiple solid cancers, and its ablation enhanced MHC-I AP and reduced tumor growth in a CD8+ T cell-dependent manner. Mechanistically, SUSD6 forms a trimolecular complex with TMEM127 and MHC-I, which recruits WWP2 for MHC-I ubiquitination and lysosomal degradation. Together with the SUSD6/TMEM127/WWP2 gene signature, which negatively correlates with cancer survival, our findings define a membrane-associated MHC-I inhibitory axis as a potential therapeutic target for both leukemia and solid cancers.
PMID: 37557169
ISSN: 1097-4172
CID: 5602312

Molecular Profiles of Noninvasive, Minimally Invasive, and Invasive Follicular Patterned Thyroid Neoplasms with Papillary Nuclear Features

Brandler, Tamar C; Zhou, Fang; Liu, Cheng Z; Serrano, Antonio; Sun, Wei; Nikiforov, Yuri E; Hodak, Steven P
PMID: 37014083
ISSN: 1557-9077
CID: 5540792

Case Report: Giant Thyroid Angiolipoma-Challenging Clinical Diagnosis and Novel Genetic Alterations

Wilkins, Reid; Zan, Elcin; Leonardi, Olga; Patel, Kepal N; Jacobson, Adam S; Jour, George; Liu, Cheng Z; Zhou, Fang
BACKGROUND:A 64-year-old man presented with a 7.8 cm lipomatous thyroid mass discovered on magnetic resonance imaging. METHODS:After two non-diagnostic fine needle aspirations (FNAs) were performed, computed tomography (CT) revealed features concerning for malignancy including central necrosis and infiltrative borders. A third FNA was still non-diagnostic. Total thyroidectomy was performed. RESULTS:Upon pathologic examination, the final diagnosis was primary thyroid angiolipoma. The lesion contained central fat necrosis with ischemic features, attributable to the FNAs. CONCLUSION/CONCLUSIONS:Ours is the third published case report of this rare entity. To date, no lipomatous thyroid tumor has undergone extensive genomic testing. Next-generation sequencing of our case revealed multiple genetic alterations, supporting the concept of angiolipomas being true neoplasms. Whereas the two previously reported cases in the literature were radiographically much smaller and appeared indolent, the large tumor in our case exhibited radiographic features concerning for liposarcoma, which belied the benign final pathologic diagnosis. Our case demonstrates that conservative surgical management (partial thyroidectomy) may be considered for lipomatous thyroid tumors, with further interventions to be determined only after final pathologic diagnosis.
PMID: 36255668
ISSN: 1936-0568
CID: 5360392

Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP) (Milan IVB) and its Subgroups: Analysis of Risk of Neoplasm and Malignancy [Meeting Abstract]

Hindi, Issa; Brandler, Tamar; Belovarac, Brendan; Szeto, Oliver; Hernandez, Osvaldo; Sun, Wei; Liu, Cheng; Zhou, Fang; Simsir, Aylin
ISI:000990969800333
ISSN: 0023-6837
CID: 5525452

Reply to "In Reference to: Non-Squamous Cell Malignancies of the Larynx" [Letter]

Rotsides, Janine M; Gordon, Alex; Oliver, Jamie R; Patel, Evan; Liu, Cheng; Givi, Babak
PMID: 35906895
ISSN: 1531-4995
CID: 5277112

Minor Salivary Gland Biopsy in Diagnosis of Sjögren's Syndrome

Gordon, Alex J; Patel, Aneek; Zhou, Fang; Liu, Cheng; Saxena, Amit; Rackoff, Paula; Givi, Babak
Objective/UNASSIGNED:Previous studies have questioned the safety and efficacy of minor salivary gland biopsy in the diagnosis of Sjögren's syndrome, citing complications and difficulty of pathologic evaluation. This study aims to determine the rate of biopsy specimen adequacy and the risk of complications after minor salivary gland biopsy. Study Design/UNASSIGNED:Case series. Setting/UNASSIGNED:Single tertiary care center. Methods/UNASSIGNED:sample were considered positive. Results/UNASSIGNED:We identified 110 patients who underwent minor salivary gland biopsy. Ninety-three (85%) were female, and the median age was 49.1 years (range, 18.7-80.5). Seventy-seven procedures (70%) were performed in the office setting, and 33 (30%) were performed in the operating room. Nearly all biopsy samples (n = 108, 98%) were adequate, and 33 (31%) were interpreted as positive. Four patients (4%) experienced temporary lip numbness, which resolved with conservative management. No permanent complications were reported after lip biopsy. Nineteen (58%) patients with positive biopsy results had no Sjögren's-specific antibodies. Most patients with positive biopsy results (n = 20, 61%) subsequently started immunomodulatory therapy. Conclusion/UNASSIGNED:Minor salivary gland biopsy can be performed safely and effectively in both the office and the operating room. This procedure provides clinically meaningful information and can be reasonably recommended in patients suspected to have Sjögren's syndrome.
PMCID:9326841
PMID: 35909442
ISSN: 2473-974x
CID: 5287772

Oral cancer induced TRPV1 sensitization is mediated by PAR2 signaling in primary afferent neurons innervating the cancer microenvironment

Scheff, Nicole N; Wall, Ian M; Nicholson, Sam; Williams, Hannah; Chen, Elyssa; Tu, Nguyen H; Dolan, John C; Liu, Cheng Z; Janal, Malvin N; Bunnett, Nigel W; Schmidt, Brian L
Oral cancer patients report sensitivity to spicy foods and liquids. The mechanism responsible for chemosensitivity induced by oral cancer is not known. We simulate oral cancer-induced chemosensitivity in a xenograft oral cancer mouse model using two-bottle choice drinking and conditioned place aversion assays. An anatomic basis of chemosensitivity is shown in increased expression of TRPV1 in anatomically relevant trigeminal ganglion (TG) neurons in both the xenograft and a carcinogen (4-nitroquinoline 1-oxide)-induced oral cancer mouse models. The percent of retrograde labeled TG neurons that respond to TRPV1 agonist, capsaicin, is increased along with the magnitude of response as measured by calcium influx, in neurons from the cancer models. To address the possible mechanism of TRPV1 sensitivity in tongue afferents, we study the role of PAR2, which can sensitize the TRPV1 channel. We show co-expression of TRPV1 and PAR2 on tongue afferents and using a conditioned place aversion assay, demonstrate that PAR2 mediates oral cancer-induced, TRPV1-evoked sensitivity in an oral cancer mouse model. The findings provide insight into oral cancer-mediated chemosensitivity.
PMCID:8904826
PMID: 35260737
ISSN: 2045-2322
CID: 5183522

Nodal Metastases in Pediatric and Adult Acinic Cell Carcinoma of the Major Salivary Glands

Dublin, Jared C; Oliver, Jamie R; Tam, Moses M; Persky, Michael J; Jacobson, Adam S; Liu, Cheng; Hu, Kenneth S; Vaezi, Alec E; Morris, Luc G T; Givi, Babak
OBJECTIVE:Acinic cell carcinoma (AciCC) is a rare, usually low-grade salivary malignancy. Evidence on rates of lymph node metastases (LNMs) is limited in pediatric patients and varies significantly (4%-45%) in adults. We set out to determine and compare rates of LNMs in pediatric and adult AciCC and to analyze their impact on survival, using the National Cancer Database. STUDY DESIGN/METHODS:Historical cohort study. SETTING/METHODS:National Cancer Database. METHODS:All AciCCs of the major salivary glands with complete clinical and pathologic nodal staging were selected between 2010 and 2016. Patient demographics, tumor characteristics, treatment, and survival were analyzed. Univariable and multivariable regression were performed to determine factors associated with LNMs and survival. RESULTS:< .001) were associated with LNM in adult patients. CONCLUSION/CONCLUSIONS:LNMs in AciCC of the major salivary glands are rare in children and adults. However, high-grade and T3-T4 tumors are associated with an increased risk of LNM. LNM is associated with worse survival.
PMID: 35259039
ISSN: 1097-6817
CID: 5183472

Endoscopic Transcanal and Transmastoid Laser-Assisted Resection of Middle Ear Capillary Hemangioma

Patel, Evan J; Deep, Nicholas L; Liu, Cheng Z; Jethanamest, Daniel
OBJECTIVE:To present a rare case of a middle ear capillary hemangioma in an adult. PATIENT/METHODS:A 31-year-old woman with a 6-month history of left ear fullness, pressure, tinnitus, and progressive hearing loss. INTERVENTION/METHODS:Endoscopic laser-assisted resection. MAIN OUTCOME MEASURES/METHODS:Clinical, radiographic, and histopathological findings of a capillary hemangioma. RESULTS:Otoscopy revealed an erythematous and slightly pulsating multilobulated middle ear retrotympanic mass. Her audiogram demonstrated a left-sided mixed hearing loss with air-conduction thresholds in the severe-to-profound range. Computed tomography (CT) imaging was significant for total opacification of the left middle ear and mastoid air cells. She underwent a combined endoscopic transcanal and transmastoid excision of the mass with ossicular chain reconstruction. A KTP laser was used to ablate and shrink down the periphery of the lesion. Pathology of the specimen was consistent with a capillary hemangioma. The patient's pulsatile tinnitus and spontaneous vertigo resolved postoperatively. CONCLUSIONS:Capillary hemangiomas are an uncommon cause of vascular middle ear lesions in adults and typically present with symptoms of aural fullness, pulsatile tinnitus, conductive hearing loss, otalgia, and vertigo. Surgery resection provides definitive treatment and the use of laser ablation techniques can allow for hemostasis and excellent visualization.
PMID: 34711778
ISSN: 1537-4505
CID: 5042762

Follicular dendritic cell sarcoma of the cervical lymph node diagnosed on fine needle aspiration cytology [Case Report]

Xia, Rong; Shafizadeh, Negin; Brandler, Tamar; Liu, Cheng; Oweity, Thaira
Follicular dendritic cell sarcomas (FDCS) are rare tumours of lymph nodes and extranodal tissues which are grouped with the histiocytic and dendritic cell neoplasms. The diagnosis is usually made after thorough clinical and pathological examination with immunohistochemical analysis. Difficulties persist in diagnosing FDCS on cytological preparations. We report herein a case of a 57-year-old female who presented with a right neck mass of 5 months duration. Computed Tomography (CT) imaging of the neck reported a necrotic right level IIb lymph node and asymmetric fullness of the right palatine tonsil. Fine needle aspiration (FNA) biopsy revealed numerous spindle, oval and stellate neoplastic cells, arranged singly and in syncytia with moderate nuclear pleomorphism, vesicular chromatin pattern, and prominent nucleoli, sprinkled with small lymphocytes. The tumour cells were strongly diffusely positive for CD21, CD23, and D2-40 immunostaining on cell bock sections, but were negative for CD1a and CD34, supporting the diagnosis of FDCS. Follow-up surgical pathology on the resection showed histopathological features and an immunohistochemical profile consistent with FDCS.
PMID: 34351024
ISSN: 1365-2303
CID: 4988692