Expression status of PD-L1 and B7-H3 in mesothelioma

Our plain-English summary of Expression status of PD-L1 and B7-H3 in mesothelioma, by E. Matsumura, K. Kajino, M. Abe, et al (Pathology International, 2020).

The study

• Authors: E. Matsumura, K. Kajino, M. Abe, N. Ohtsuji, H. Saeki, M.T. Hlaing, O. Hino
• Journal: Pathology International
• Published: 2020;70(12):999-1008
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelioma is a rare, aggressive malignancy with poor outcome, and has limited treatment options. The aim of this study was to perform a comprehensive analysis of programmed death ligand 1 (PD-L1) and B7 homolog 3 (B7-H3) expression in mesothelioma. We investigated the protein expression of PD-L1 and B7-H3 and their potential correlation with histological subtype, which might help to develop new therapies targeting these immune checkpoint molecules. Expression analysis of PD-L1 and B7-H3 was performed by immunohistochemistry using serial tissue sections of specimens obtained from 31 patients with mesothelioma. Tumors were classified into 22 epithelioid, 6 sarcomatoid, and 3 biphasic types. Of the 31 patients, 13 (41.9%) were positive for PD-L1 and 28 (90.3%) were B7-H3 positive. Twelve of the 13 PD-L1 positive patients were positive for B7-H3. PD-L1 and B7-H3 were widely co-expressed in biphasic and sarcomatoid type tumor cells. These findings might provide a rationale for the use of combination therapy for mesothelioma by targeting PD-L1 and B7-H3, as well as the development of anti-B7-H3 or anti-PD-L1 single agents.

© 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

In plain English

This laboratory study stained tumor tissue from 31 Japanese patients with mesothelioma for two immune checkpoint proteins, PD-L1 and B7-H3. The tissue was collected by surgery, biopsy or autopsy between 1991 and 2019. There were 22 epithelioid, 3 biphasic and 6 sarcomatoid tumors. PD-L1 was found in 13 of 31 patients (41.9%). That was 6 of 22 epithelioid cases (27.3%) versus 7 of 9 non-epithelioid cases (77.8%), a statistically significant difference. B7-H3 was found in 28 of 31 (90.3%), at similar rates across subtypes, and 12 of the 13 PD-L1-positive cases also had B7-H3. Two samples of non-tumorous mesothelial tissue showed neither protein. Fifteen patients had a recorded history of asbestos exposure, 5 had none, and for 11 it was unknown. Among the 9 non-epithelioid cases, all 7 men were PD-L1 positive and 5 of them had asbestos exposure. The authors called this a tendency that was not statistically significant because the numbers were small. The authors concluded that the findings might support therapies targeting PD-L1 and B7-H3. They noted that no B7-H3 drug is approved and that positivity criteria are not defined for mesothelioma.

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 of archived tumor tissue using immunohistochemistry (staining of serial tissue sections), plus flow cytometry on mesothelioma cell lines
• Who was studied: Tissue from 31 Japanese patients diagnosed with mesothelioma (22 epithelioid, 3 biphasic, 6 sarcomatoid), obtained by surgical resection, biopsy or autopsy between 1991 and 2019 at Juntendo University, Tokyo. Also 2 non-tumorous mesothelial tissue samples from autopsies of patients with other cancers. Mean age at diagnosis 66.1 years; 24 men, 7 women.
• Exposure: The study measured two tumor proteins (PD-L1 and B7-H3), not an exposure. History of asbestos exposure was recorded: exposed 15 (48.4%), never exposed 5 (16.1%), unknown 11 (35.5%). No fiber types, products, jobs or doses are given.
• Main results:
  • PD-L1 was positive (at least 1% of tumor cells stained) in 13 of 31 patients (41.9%).
  • PD-L1 positivity was significantly higher in non-epithelioid (biphasic and sarcomatoid) cases, 7 of 9 (77.8%), than in epithelioid cases, 6 of 22 (27.3%); P = 0.00969.
  • B7-H3 was positive in 28 of 31 patients (90.3%). Rates were similar in epithelioid cases (20 of 22, 90.9%) and non-epithelioid cases (8 of 9, 88.9%); P = 0.86289.
  • Twelve of the 13 PD-L1-positive cases were also B7-H3 positive.
  • Non-tumorous mesothelial tissue did not show membrane staining for either PD-L1 or B7-H3.
  • In epithelioid tumors, the stained area for B7-H3 was significantly larger than for PD-L1 (P less than 0.00001). In non-epithelioid tumors there was no significant difference (P = 0.46815).
  • Among the 9 non-epithelioid cases, all 7 men were PD-L1 positive. Five of them had a history of asbestos exposure and 2 had unknown exposure. Both women were PD-L1 negative. The authors reported no such relationship in the 22 epithelioid cases.
  • In flow cytometry, four mesothelioma cell lines and one non-tumorous mesothelial cell line (MeT-5A) expressed B7-H3.
• The authors' conclusion: The authors concluded that the findings might provide a rationale for combination therapy targeting PD-L1 and B7-H3 in mesothelioma, and for developing single-agent drugs against either protein.
• Limitations the authors state:
  • None of the drugs being developed to target B7-H3 has been approved by regulators.
  • There are currently no clinical trials of these drugs in mesothelioma, so effectiveness by histologic type is unknown.
  • Criteria for counting a mesothelioma as PD-L1 or B7-H3 positive have not been defined.
  • The apparent link between PD-L1 and asbestos exposure history in non-epithelioid cases was not statistically significant because of the small number of cases.

Topics

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

Medical terms in this study, explained in our Lexicon: PD-L1, Mesothelioma, Histological Subtype, Immunohistochemistry, Epithelioid, Sarcomatoid, Biphasic Mesothelioma.

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