HLA Expression Correlates to the Risk of Immune Checkpoint Inhibitor-Induced Pneumonitis

Pierpaolo Correale, Rita Emilena Saladino, Diana Giannarelli, Andrea Sergi, Maria Antonietta Mazzei, Giovanna Bianco, Rocco Giannicola, Eleonora Iuliano, Iris Maria Forte, Natale Daniele Calandruccio, Antonia Consuelo Falzea, Alessandra Strangio, Valerio Nardone, Pierpaolo Pastina, Paolo Tini, Amalia Luce, Michele Caraglia, Daniele Caracciolo, Luciano Mutti, Pierfrancesco TassoneLuigi Pirtoli, Antonio Giordano, Pierosandro Tagliaferri

Research output: Contribution to journalArticle

Abstract

Tumor-infiltrating T cell rescue by programmed cell death receptor-1 (PD-1)/PD-1 ligand-1 (PD-L1) immune checkpoint blockade is a recommended treatment for malignant diseases, including metastatic non-small-cell lung cancer (mNSCLC), malignant melanoma (MM), head and neck, kidney, and urothelial cancer. Monoclonal antibodies (mAbs) against either PD-1 or PD-L1 are active agents for these patients; however, their use may be complicated by unpredictable immune-related adverse events (irAEs), including immune-related pneumonitis (IRP). We carried out a retrospective multi-institutional statistical analysis to investigate clinical and biological parameters correlated with IRP rate on a cohort of 256 patients who received real-world treatment with PD-1/PD-L1 blocking mAbs. An independent radiological review board detected IRP in 29 patients. We did not find statistical IRP rate correlation with gender, tumor type, specific PD-1 or PD-L1 blocking mAbs, radiation therapy, inflammatory profile, or different irAEs. A higher IRP risk was detected only in mNSCLC patients who received metronomic chemotherapy +/- bevacizumab compared with other treatments prior PD-1/PD-L1 blockade. Moreover, we detected a strong correlation among the IRP rate and germinal expression of HLA-B*35 and DRB1*11, alleles associated to autoimmune diseases. Our findings may have relevant implications in predicting the IRP rate in mNSCLC patients receiving PD-1/PD-L1 blockade and need to be validated on a larger patient series.

Original languageEnglish
JournalCells
Volume9
Issue number9
DOIs
Publication statusPublished - Aug 25 2020

Keywords

  • cancer immunotherapy
  • HLA-profile
  • immune-related pneumonitis
  • irAEs
  • PD-1/PD-L1 blockade

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Correale, P., Saladino, R. E., Giannarelli, D., Sergi, A., Mazzei, M. A., Bianco, G., Giannicola, R., Iuliano, E., Forte, I. M., Calandruccio, N. D., Falzea, A. C., Strangio, A., Nardone, V., Pastina, P., Tini, P., Luce, A., Caraglia, M., Caracciolo, D., Mutti, L., ... Tagliaferri, P. (2020). HLA Expression Correlates to the Risk of Immune Checkpoint Inhibitor-Induced Pneumonitis. Cells, 9(9). https://doi.org/10.3390/cells9091964