Heterogeneity in PD-L1 expression in malignant peritoneal mesothelioma with systemic or intraperitoneal chemotherapy

Our plain-English summary of Heterogeneity in PD-L1 expression in malignant peritoneal mesothelioma with systemic or intraperitoneal chemotherapy, by M.G. White, J.J. Schulte, L. Xue, et al (British Journal of Cancer, 2021).

The study

• Authors: M.G. White, J.J. Schulte, L. Xue, Y. Berger, D. Schuitevoerder, C.C. Vining, H.L. Kindler, A. Husain, K.K. Turaga, O.S. Eng
• Journal: British Journal of Cancer
• Published: 2021;124(3):564-566
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Programmed death-ligand 1 (PD-L1) expression has been described in patients with malignant peritoneal mesothelioma (MPM), but treatment strategies utilising immune checkpoint inhibition are yet to be defined. Here, we examine levels of PD-L1 expression in MPM patients treated with systemic and/or intraperitoneal chemotherapy using tissue from patient tumour biopsies or resections at multiple time points. We found the mean PD-L1 expression was higher in those with a germline mutation and/or those with a higher somatic mutation burden. Moreover, PD-L1 expression was lower in patients who had received prior chemotherapy as compared to the treatment-naive cohort. Twenty patients who received chemotherapy, either systemic and/or peritoneal, between PD-L1 measurements showed marked heterogeneity. Six (30%) patients demonstrated upregulation of PD-L1, while eight (40%) demonstrated downregulation. Heterogeneity in PD-L1 expression in MPM before and after cytotoxic therapies may present an additional consideration when initiating immune checkpoint inhibition in this rare and challenging disease.

In plain English

This was a retrospective review of 53 patients with malignant peritoneal mesothelioma treated at one institution, the University of Chicago, between 2017 and 2019. The authors stained 78 stored tumor samples for PD-L1, a protein targeted by some immunotherapy drugs. They compared PD-L1 levels with patient and tumor features and with prior chemotherapy. Thirty-four patients (65%) expressed PD-L1 above 1% staining, and 9 (17%) had high levels. PD-L1 was higher in samples from patients with inherited (germline) mutations (20% vs 1%, p = 0.04) and in samples with more than 1 tumor mutation per mega base pair (7.5% vs 0%, p = 0.04). It was lower in samples taken after systemic chemotherapy (6% vs 16%, p = 0.02). Twenty patients were tested both before and after chemotherapy. Among them, 6 (30%) showed an increase, 8 (40%) showed a decrease, and 7 (35%) stayed below 1% at both times. The authors concluded that PD-L1 levels can change markedly with chemotherapy and that further studies are warranted. They listed the retrospective design and possible differences between tumor sites as limitations. The article does not discuss asbestos.

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: Retrospective review of a single-institution database (brief communication)
• Who was studied: 53 patients with malignant peritoneal mesothelioma treated at a single institution (University of Chicago) between 2017 and 2019 who had banked tissue; 78 specimens in total. 20 of the patients had PD-L1 measured before and after chemotherapy.
• Exposure: The study did not examine asbestos exposure. It examined treatment with systemic chemotherapy (mostly platinum-based chemotherapy with pemetrexed) and/or hyperthermic intraperitoneal chemotherapy (HIPEC) in relation to tumor PD-L1 expression. No patients received immunotherapy.
• Main results:
  • Of 53 patients, 34 (65%) expressed PD-L1 (more than 1% staining) and 9 (17%) had high levels of PD-L1 expression
  • PD-L1 expression was higher in samples from patients with germline mutations than without (20% vs 1%, p = 0.04)
  • PD-L1 expression was higher in samples with somatic mutation burden above 1 mutation per mega base pair than in those with lower burden (7.5% vs 0%, p = 0.04)
  • Patients who received systemic chemotherapy before biopsy had lower PD-L1 expression than those with no prior chemotherapy (6% vs 16%, p = 0.02)
  • There was no difference between treatment-naive and HIPEC groups (16.1% vs 13.8%, p = 0.86). Treatment-naive patients differed from those with prior systemic chemotherapy regardless of HIPEC status (15.8% vs 5.2%, p = 0.04).
  • Among 20 patients with PD-L1 measured before and after chemotherapy: 7 (35%) had less than 1% staining at both times, 6 (30%) showed upregulation and 8 (40%) showed downregulation
  • Two patients (10%) with high (greater than 50%) staining moved to low or no staining after HIPEC, and one patient (5%) with high staining moved to low staining after systemic chemotherapy
• The authors' conclusion: The authors concluded that PD-L1 is present in a significant proportion of malignant peritoneal mesothelioma specimens, but its level can change drastically with systemic or peritoneal chemotherapy and over time. They concluded that this may need to be considered when starting immune checkpoint inhibition, and that future studies are warranted.
• Limitations the authors state:
  • Retrospective design, with the limitations inherent to it
  • Variability within the cohort in treatment timing, sequence of interventions, and timing and technique of biopsies
  • The observed heterogeneity may reflect spatial differences among different foci of peritoneal disease

Topics

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

Medical terms in this study, explained in our Lexicon: PD-L1, Peritoneal Mesothelioma, Chemotherapy, Germline Mutation, Somatic Mutation.

Related studies

• Response to Comment on "Heterogeneity in PD-L1 expression in malignant peritoneal mesothelioma with systemic or intraperitoneal chemotherapy" — M.G. White, O.S. Eng (2021)
• Comment on "Heterogeneity in PD-L1 expression in malignant peritoneal mesothelioma with systemic or intraperitoneal chemotherapy" — H. Yang, S.R.R. Hall, et al. (2021)
• Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study — S. Valmary-Degano, P. Colpart, et al. (2017)
• Malignant pleural mesothelioma: clinical experience and prognostic value of derived neutrophil-to-lymphocyte ratio and PD-L1 expression — L. Gutierrez-Sainz, P. Cruz, et al. (2021)
• Tumor PD-L1 expression in malignant pleural and peritoneal mesothelioma by Dako PD-L1 22C3 pharmDx and Dako PD-L1 28-8 pharmDx assays — D.B. Chapel, R. Stewart, et al. (2019)
• Malignant peritoneal mesothelioma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: is GLUT1 expression a major prognostic factor? A preliminary study — J. Hommell-Fontaine, S. Isaac, et al. (2013)

Browse more research in British Journal of Cancer, or return to medical research.