Spatial Landscape of Malignant Pleural and Peritoneal Mesothelioma Tumor Immune Microenvironments

Details

• Personal Author:
  Becich MJ ; Bruno TC ; Kim ES ; Lembersky D ; Ma X ; Osmanbeyoglu HU ; Testa JR
• Description:
  Immunotherapies have demonstrated limited clinical efficacy in malignant mesothelioma treatment. We conducted multiplex immunofluorescence analyses on tissue microarrays (n = 3) from patients with malignant pleural mesothelioma (MPM, n = 88) and malignant peritoneal mesothelioma (MPeM, n = 25). Our study aimed to elucidate spatial distributions of key immune cell populations and their association with lymphocyte activation gene 3 (LAG3), BRCA1-associated protein 1 (BAP1), neurofibromatosis type 2 (NF2), and methylthioadenosine phosphorylase (MTAP), with MTAP serving as a cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/B) surrogate marker. Additionally, we examined the relationship between the spatial distribution of major immune cell types and prognosis and clinical characteristics of patients with malignant mesothelioma. We observed a higher degree of interaction between immune cells and tumor cells in MPM compared with MPeM. Notably, within MPM tumors, we detected a significantly increased interaction between tumor cells and CD8+ T cells in tumors with low BAP1 expression compared with those with high BAP1 expression. To support the broader research community, we have developed The Human Spatial Atlas of Malignant Mesothelioma, containing hematoxylin and eosin and multiplex immunofluorescence images with corresponding metadata. Significance: Considering the limited therapeutic options available to patients with malignant mesothelioma, there is substantial translational potential in understanding the correlation between the spatial architecture of the malignant mesothelioma tumor immune microenvironment and tumor biology. Our investigation reveals critical cell-cell interactions that may influence the immune response against malignant mesothelioma tumors, potentially contributing to the differential behaviors observed in MPM and MPeM. These findings represent a valuable resource for the malignant mesothelioma cancer research community. [Description provided by NIOSH]
• Subjects:
  Immune System Neoplasms Occupational Health Safety
• Keywords:
  Cancer Cell Type Immune Reaction Malignancy Mesothelioma Tumors
• ISSN:
  2767-9764
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  4
• Issue:
  8
• NIOSHTIC Number:
  nn:20070026
• Citation:
  Cancer Res Commun 2024 Aug; 4(8):2133-2146
• Contact Point Address:
  Hatice U. Osmanbeyoglu, University of Pittsburgh School of Medicine, 5051 Centre Avenue, Pittsburgh, PA 15213
• Email:
  osmanbeyogluhu@pitt.edu
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Construction ; Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20060901
• Source Full Name:
  Cancer Research Communications
• End Date:
  20260831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:32a7d795157cfb28b3851caaa305a379d086488d11294e9ec69ed7c6ddc96fc71ea3caebb0755a976fe61e6fcf6e8da9117600fee2d11bbe2f33b0c5ee116d38
• Download URL:
  https://stacks.cdc.gov/view/cdc/208331/cdc_208331_DS1.pdf
• File Type:
  [PDF - 29.05 MB ]