Evidence of Tumour Microenvironment and Stromal Cellular Components in Retinoblastoma

Raguraman, Rajeswari; Parameswaran, Sowmya; Kanwar, Jagat R.; Khetan, Vikas; Rishi, Pukhraj; Kanwar, Rupinder K.; Krishnakumar, Subramanian

doi:10.1159/000488709

Cited by 14 publications

(15 citation statements)

References 53 publications

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“…6,7 The TME of RB is still sparsely explored. [8][9][10][11][12][13][14][15][16][17][18][19][20] There are only few investigations on the impact of CHT on RB TME. [16][17][18][19][20] In the present study, in a cohort of 94 patients who underwent enucleation for RB, we investigated the following elements at the tumor tissue level: the frequency of several subsets of TI-ICs, including lymphocytes, dendritic-like cells, macrophages and myeloid-derived suppressor-like granulocytic (G-MDS-like) cells, the RB proliferation rate, the extent of gliosis, the protein expression of PD-L1 and PD-1, and the number of vessels.…”

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confidence: 99%

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1− Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy

Miracco

Toti

Gelmi

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME).CASES AND METHODS. Ninety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intraarterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for the following parameters: tumor-infiltrating inflammatory cells (TI-ICs); programmed cell death protein 1 (PD-1) positive TI-ICs; Ki67 proliferation index; gliosis; PD-1 ligand (PD-L1) protein expression; vessel number. We also correlated these TME factors with the presence of histological high-risk factors (HHRF+) and RB anaplasia grade (AG). RESULTS.After CHT, a decrease in both RB burden and Ki67 positivity was observed. In parallel, most subsets of TI-ICs, PD-1+ TI-ICs, gliosis, and PD-L1 protein expression significantly increased (P < 0.001, P = 0.02, P < 0.001, respectively). Vessel number did not significantly vary. Age, HHRFs+ and AG were significantly different between primary and chemoreduced RBs (P < 0.001, P = 0.006, P = 0.001, respectively) and were correlated with most TME factors. CONCLUSIONS.CHT modulates host antitumor immunity by reorienting the RB TME from anergic into an active, CD8+, PD-L1+ hot state. Furthermore, some clinicopathological characteristics of RB correlate with several factors of TME. Our study adds data in favor of the possibility of a new therapeutic scenario in human RB.

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confidence: 99%

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1− Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy

Miracco

Toti

Gelmi

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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“…Since, B7H3 is reported to decrease T lymphocyte recruitment into the tumour regions, we analysed the T lymphocytes distribution in different regions of RB tumour. H and E staining on primary RB tumour did not reveal a clear inflammatory component except for a few macrophages 18 . Hence, specific T lymphocyte markers such as CD3,CD4,CD8 were carried out on RB tumors (n = 12) and different regions (Tumor lobule, tumor blood vessels, Retinal blood vessel, invading front, Necrotic area) were analysed.…”

Section: T Cell Markers Cd3 Cd4 Cd8 Foxp3 In Retinoblastomamentioning

confidence: 82%

“…Invasion status of RB tumor determines the region they metastasize. The common regions of metastases are the central nervous system (CNS), regional lymph nodes, bone marrow and the bones 18 . In this study, the sites of invasion were considered as neural and non-neural due to their differences in their prognosis and the regions they metastasize.…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of B7H3 expression in retinoblastoma

Ganesan

Parameswaran²,

Sharma

et al. 2020

Sci Rep

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Retinoblastoma (RB) is the most common paediatric intraocular tumour. currently, chemotherapy is widely used to reduce the chance of metastasis as well as for vision salvage. the limitations of chemotherapy for RB include chemoresistance and cytotoxicity. Recently, immunotherapy is considered for treating chemoresistant cancers. Although, several molecular targets are available for immunotherapy in different cancers, we were interested in B7H3, as it was differentially expressed between retinoblastoma and retina in our earlier proteomics study. Hence, in this study we validated the previous finding by Western blotting and immunohistochemistry on primary RB tumor samples. The results suggest significantly increased expression of B7H3 in RB tumor samples compared to retina by western blotting. immunohistochemistry revealed spatial, inter and intratumoral heterogeneity in the primary RB tumor sections. Correlation of the B7H3 expression with clinical and histopathological data revealed significantly increased expression of B7H3 in poorly differentiated, non-neural invasive tumors and lower expression in neural invasion and severe anaplastic areas of the tumors. B7H3 expression did not significantly vary between low-risk and high-risk tumors. The study also revealed considerably reduced infiltration of T lymphocytes in RB. We conclude that B7H3 is prominently expressed in primary RB tumors and could be used for targeted therapy.

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“…In addition, the overall survival rate of the low stromal score group was more favorable compared with that of the high score group. Stromal cells provide a suitable environment for tumor growth and progression (35). Analyzing the expression profiles of genes and identifying the underlying molecular mechanisms of gene expression levels affecting the tumor matrix, promoting tumorigenesis and development may provide novel insight into the clinical diagnosis and treatment of kidney cancer.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and predictive value of immune/stromal-related gene biomarkers in renal cell carcinoma

et al. 2020

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Immune/stromal-associated genes may be promising biomarkers for cancer diagnosis and the determination of clinical cancer treatment options. The aim of the present study was to identify prognostic stromal/immune-associated genes in renal cell carcinoma (RCC). RCC gene expression data (885 cases) were obtained from The Cancer Genome Atlas database. Immune/stromal scores were calculated by using the ESTIMATE package in R. Immune/stromal scores were significantly associated with Tumor-Node-Metastasis stage, clinical stage and overall survival rate (P<0.05). There were 419 differentially expressed genes (DEGs) based on immune scores and 738 DEGs based on stromal scores. Among these DEGs, 406 DEGs based on stromal scores and 252 DEGs based on immune scores were significantly associated with overall survival rate (P<0.05). The biological functions of these DEGs were primarily enriched in the 'immune response' and 'regulation of cell migration and proliferation'. These DEGs were observed in a protein-protein interaction network. A LASSO Cox regression model was used to build a prognostic 6 gene-based classifier, including the IL21R, ATP6V1C2, GBP1, P2RY10, GBP4 and TNNC2 genes [area under the curve (AUC) =0.776]. The predictive model which combined this classifier with clinical prognostic factors had a high accuracy in predicting patient survival in RCC (combined AUC =0.899). Taken together, these results demonstrated that there are significant associations between immune/stromal scores and clinicopathological staging. A set of tumor microenvironmentassociated genes that have powerful prognostic value in patients with RCC were identified in the present study.

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Evidence of Tumour Microenvironment and Stromal Cellular Components in Retinoblastoma

Cited by 14 publications

References 53 publications

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1− Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1− Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy

Clinical relevance of B7H3 expression in retinoblastoma

Prognostic and predictive value of immune/stromal-related gene biomarkers in renal cell carcinoma

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