Augmentation of tumor expression of HLA-DR, CXCL9, and CXCL10 may improve olfactory neuroblastoma immunotherapeutic responses.

BACKGROUND: Olfactory neuroblastoma is a rare malignancy of the anterior skull base typically treated with surgery and adjuvant radiation. Although outcomes are fair for low-grade disease, patients with high-grade, recurrent, or metastatic disease oftentimes respond poorly to standard treatment methods. We hypothesized that an in-depth evaluation of the olfactory neuroblastoma tumor immune microenvironment would identify mechanisms of immune evasion in high-grade olfactory neuroblastoma as well as rational targetable mechanisms for future translational immunotherapeutic approaches. METHODS: Multispectral immunofluorescence and RNAScope evaluation of the tumor immune microenvironment was performed on forty-seven clinically annotated olfactory neuroblastoma samples. A retrospective chart review was performed and clinical correlations assessed. RESULTS: A significant T cell infiltration was noted in olfactory neuroblastoma samples with a stromal predilection, presence of myeloid-derived suppressor cells, and sparse natural killer cells. A striking decrease was observed in MHC-I expression in high-grade olfactory neuroblastoma compared to low-grade disease, representing a mechanism of immune evasion in high-grade disease. Mechanistically, the immune effector stromal predilection appears driven by low tumor cell MHC class II (HLA-DR), CXCL9, and CXCL10 expression as those tumors with increased tumor cell expression of each of these mediators correlated with significant increases in T cell infiltration. CONCLUSION: These data suggest that immunotherapeutic strategies that augment tumor cell expression of MHC class II, CXCL9, and CXCL10 may improve parenchymal trafficking of immune effector cells in olfactory neuroblastoma and augment immunotherapeutic responses.

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

BACKGROUND: Programmed cell death ligand 1 (PD-L1) is a transmembrane glycoprotein that interacts with the receptor programmed cell death 1 (PD-1) to suppress T-cell activation, reduce adjacent tissue damage, and promote tolerance to self-antigens. Tumors may express PD-L1 as a mechanism to evade immune detection. Recent clinical trials have demonstrated the efficacy of PD-L1/PD-1 antagonists through activation of tumor-infiltrated CD8+ T cells. The aim of this study was to determine the expression pattern of PD-L1 and PD-1 in olfactory neuroblastoma (ONB) tumor cells and to determine the presence of PD-1+ and CD8+ lymphocytes in the ONB immune microenvironment. METHODS: Immunohistochemistry for expression of PD-L1, PD-1, and CD8 was performed on paraffin-embedded ONB tissue. RESULTS: Of the 10 primary site ONB samples, 4 demonstrated positive PD-L1 expression. Of PD-L1+ tumors, the 2 highest expressing samples were found to contain PD-1+ tumor cells. Of the 4 available metastatic samples, all of which arose from PD-L1- primary site ONB, 3 were positive for PD-L1 and contained PD-1+ tumor cells. PD-L1+ primary and metastatic tumors also demonstrated increased PD-1+ infiltrating lymphocytes in the tumor and stroma (11.6- and 4.62-fold increase) compared with PD-L1- samples (P < 0.05 and P = 0.068 respectively). PD-L1+ specimens demonstrated increased CD8+ lymphocytes in the tumor and stroma (7.46- and 2.14-fold increase) compared with PD-L1- tumors (P < 0.05 for both). CONCLUSIONS: These data demonstrate that a proportion of ONB primary and metastatic tumors express PD-L1 and possess an associated tumor and stromal infiltrate of PD-1+ and CD8+ lymphocytes.

[Sinonasal teratocarcinosarcoma: clinicopathologic study and analysis].

OBJECTIVE: To study the clinicopathologic features, immunophenotype, diagnosis and differential diagnosis of Sinonasal teratocarcinosarcoma (SNTCS). METHOD: The clinical findings, morphologic features and immunohistochemical markers in one case of SNTCS were studied, and the relevant literatures were reviewed. RESULT: The Tumor tissue is composed of three layers, with mature and immature squamous epithelium nests, neural epithelial cells and olfactory neuroblastoma-like cells derived of ectoderm; Sarcomatoid components and bone tissue derived of mesoderm; The glandular and tubular structures part of which is adenocarcinoma and respiratory epithelium derived of endoderm; The fetal clear cell squamous epithelium is typical. In addition, diffuse large cytoplasm-with high light and cytoplasm with dark light has no obviously boundery. Immunohistochemical staining showed immune markers of different germ layers corresponding, squamous epithelium, glandular epithelium and respiratory epithelium were positive for CK and EMA, neural epithelial cells and olfactory neuroblastoma-like cells were positive for S-100, NSE and Syn, sarcomatoid area was positive for Vim, light dye area was positive for Vim, CD99 and CK, dark area was positive for NSE and GFAP. CONCLUSION: SNTCS is a rare malignant tumor with the features of teratoma and carcinosarcoma, its histopathological and immunohistochemical features were typical, should be more drawn and sliced to avoid misdiagnosis and missed diagnosis.

CD31 immunoreactivity in small round cell tumors.

CD31 has been shown to be a sensitive and specific marker for endothelial differentiation among epithelioid and spindled-pleomorphic human neoplasms. However, the role of this marker in the evaluation of small round cell tumors has not been evaluated. Formalin-fixed, paraffin-embedded tissue sections from 276 small round cell tumors, including 85 Ewing's sarcoma/primitive neuroectodermal tumors (ES/PNET), 52 rhabdomyosarcomas, 10 extraabdominal polyphenotypic small cell tumors, six desmoplastic small cell tumors, 11 neuroblastomas, 23 Wilms' tumors, 20 retinoblastomas, 13 esthesioneuroblastomas, and 56 small cell malignant lymphomas were stained with CD31 (JC/70A, 1:40), using a modified avidinbiotin-peroxidase complex technique, after citrate buffer microwave epitope retrieval. Among nonlymphoid small round cell tumors, four of 85 ES/PNET were at least focally reactive. No other lesion in this group was positive. In contrast, the majority of well-differentiated (11 of 17), intermediately differentiated (two of three), and lymphoblastic lymphomas (three of three) were positive. Small cleaved lymphomas (three of 13 follicular, one of 13 diffuse) were less often reactive, whereas small noncleaved lesions were negative. Although reactivity for CD31 in ES/PNET is uncommon, the presence of platelet/endothelial cell adhesion molecule in a small cell neoplasm should not in isolation be taken as evidence of hematopoietic origin. These results further define the utility of CD31 in the evaluation of human neoplasms.