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HLA Expression Correlates to the Risk of Immune Checkpoint Inhibitor-Induced Pneumonitis
Correale, Pierpaolo Saladino, Rita Emilena Giannarelli, Diana Sergi, Andrea Mazzei, Maria Antonietta Bianco, Giovanna Giannicola, Rocco Iuliano, Eleonora Forte, Iris Maria Calandruccio, Natale Daniele
Correale, Pierpaolo
Saladino, Rita Emilena
Giannarelli, Diana
Sergi, Andrea
Mazzei, Maria Antonietta
Bianco, Giovanna
Giannicola, Rocco
Iuliano, Eleonora
Forte, Iris Maria
Calandruccio, Natale Daniele
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2020-08-25
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http://doi.org/10.3390/cells9091964
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.
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Correale P, Saladino RE, Giannarelli D, Sergi A, Mazzei MA, Bianco G, Giannicola R, Iuliano E, Forte IM, Calandruccio ND, Falzea AC, Strangio A, Nardone V, Pastina P, Tini P, Luce A, Caraglia M, Caracciolo D, Mutti L, Tassone P, Pirtoli L, Giordano A, Tagliaferri P. HLA Expression Correlates to the Risk of Immune Checkpoint Inhibitor-Induced Pneumonitis. Cells. 2020; 9(9):1964.
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