Expression and regulation of B7-H3 immunoregulatory receptor, in human mesothelial and mesothelioma cells: immunotherapeutic implications

Our plain-English summary of Expression and regulation of B7-H3 immunoregulatory receptor, in human mesothelial and mesothelioma cells: immunotherapeutic implications, by L. Calabrò, L. Sigalotti, E. Fonsatti, et al (Journal of Cellular Physiology, 2011).

The study

• Authors: L. Calabrò, L. Sigalotti, E. Fonsatti, E. Bertocci, A.M. Di Giacomo, R. Danielli, O. Cutaia, F. Colizzi, A. Covre, L. Mutti, P.G. Natali, M. Maio
• Journal: Journal of Cellular Physiology
• Published: 2011;226(10):2595-600
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

No treatment prolongs the survival of malignant mesothelioma (MM) patients. Since MM elicits anti-tumor host's immune responses, immunotherapy represents a promising strategy for its control. Immunomodulatory antibodies against components of the B7 family of immunomodulatory molecules that regulate T cell activation are being investigated in human malignancies including MM. The expression of B7-H3, a new component of the B7 family was investigated in primary cultures of human mesothelial cells (HMC) and in MM cell lines by flow cytometry and molecular analyses, and in MM tissues by immunohistochemistry. The role of DNA hypomethylating agents in modulating levels of B7-H3 expression in MM cells was also studied. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that B7-H3 mRNA was consistently detectable in mesothelial and MM cells investigated; however, real-time quantitative RT-PCR analyses showed highly heterogeneous levels of B7-H3 mRNA among investigated MM cells. The analysis of B7-H3 protein expression indicated that comparable levels of B7-H3 were expressed on both cell types. Treatment with the DNA hypomethylating agent 5-aza-2'-deoxycytidine did not significantly affect the expression of B7-H3 mRNA in MM cells. In vivo, while B7-H3 was expressed in all 13 tumor biopsies of the epithelial variant, with high levels in 54% of cases, it was rarely detectable in spindle type MM in which 1/5 biopsies weakly expressed B7-H3. These findings suggest that B7-H3 is a promising target for new immunotherapeutic strategies in MM, with particular emphasis in the epithelial variant.

Copyright © 2010 Wiley-Liss, Inc.

In plain English

This was a laboratory study of B7-H3, a protein that helps regulate immune T cells and was being considered as a target for antibody treatments. The authors measured B7-H3 in three kinds of samples. The first was normal human mesothelial cells taken from the pleural fluid of patients with heart failure. The second was nine malignant mesothelioma cell lines (seven epithelioid, two sarcomatoid). The third was a tissue array of 23 mesothelioma samples (13 epithelial, 5 mixed, 5 sarcomatoid). The study did not examine asbestos exposure. B7-H3 mRNA was found in all the mesothelial and mesothelioma cells studied, though levels varied among the mesothelioma lines. The protein was present on normal and cancer cells in culture. The drug 5-aza-2'-deoxycytidine did not significantly change B7-H3 mRNA levels in the mesothelioma lines, except for a 2.3-fold rise in one line, MPP-89. In tissue, all 13 epithelial tumors expressed B7-H3, 7 of them at high levels. Only 1 of 5 sarcomatoid tumors was positive, at moderate intensity. The authors concluded that B7-H3 may be an additional therapeutic target for mesothelioma. They noted that low levels in sarcomatoid tumors might fall below their test's sensitivity.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study: cultured cells (in vitro) and tumor tissue samples stained by immunohistochemistry (in vivo)
• Who was studied: Seven epithelioid and two sarcomatoid malignant mesothelioma cell lines; primary human mesothelial cells from the pleural effusions of patients with heart failure; a purchased tissue microarray of 23 mesothelioma samples (13 epithelial, 5 mixed, 5 sarcomatoid) plus three normal pleural tissues; and four full tumor sections from Rome. Healthy-donor blood cells (PBMC) and a neuroblastoma cell line served as negative and positive controls.
• Exposure: No asbestos exposure was studied. Mesothelioma cell lines were treated in the laboratory with the DNA hypomethylating drug 5-aza-2'-deoxycytidine (5-AZA-CdR).
• Main results:
  • B7-H3 mRNA was detected in all mesothelioma cell lines tested and in the normal mesothelial cells
  • Quantitative testing showed widely varying B7-H3 mRNA levels among the mesothelioma cell lines, with a 9.6-fold difference between the MPP-89 and MES-2 lines
  • Normal mesothelial cells expressed B7-H3 mRNA at levels comparable to most of the mesothelioma cell lines
  • 5-AZA-CdR did not significantly change B7-H3 mRNA expression, measured by quantitative RT-PCR, in the mesothelioma cell lines, except for a 2.3-fold increase in MPP-89 cells
  • B7-H3 protein was found on the cell surface of normal and cancerous mesothelial cells in culture (98 to 100% positive cells in each line). Levels were broadly comparable, with the highest levels in MES-2 (epithelial, MFI 1,353) and MES-OC-99 (sarcomatoid, MFI 658).
  • In the tissue microarray, all 13 epithelial mesotheliomas expressed B7-H3, 7 of 13 (54%) with the high score
  • Only one of five sarcomatoid tumors was B7-H3 positive, with moderate staining intensity
  • In mixed tumors, staining was restricted to the epithelial component
  • Normal-appearing pleural cells and two specimens classified as benign mesothelioma showed only weak B7-H3 expression
  • None of the tumor samples, of any histologic type, contained lymphatic cell infiltrates
• The authors' conclusion: The authors concluded that their data suggest B7-H3 may be an additional therapeutic target for developing immunotherapy for mesothelioma patients, particularly in the epithelial type
• Limitations the authors state:
  • The authors could not exclude that low levels of B7-H3 are present in sarcomatoid tumors below the sensitivity of their testing method
  • No disease stage data were available for the tissue microarray samples
  • The higher expression in epithelial tumors seen in tissue was not fully reflected in the cell culture testing

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Immunotherapy, Mesothelial Cells, Immunohistochemistry.

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