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

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.

Genome-Wide B Cell, CD4+, and CD8+ T Cell Epitopes That Are Highly Conserved between Human and Animal Coronaviruses, Identified from SARS-CoV-2 as Targets for Preemptive Pan-Coronavirus Vaccines

“…The polymorphic HLA molecules can be clustered into a handful of HLA-A supertypes that bind largely overlapping peptide repertoires (76). Moreover, such a multiepitope vaccine would be easily adapted to exclude undesirable epitopes that are restricted to HLA-B*44 and HLA-C*01 alleles, which appear to correlate with SARS-CoV-2 virus spreading across certain countries (77), and HLA-B*35 allele, which appear to be associated with severe pneumonia developed by SARS-CoV-2 in young patients (78).…”

JNJ-64041757 (JNJ-757), a Live, Attenuated, Double-Deleted Listeria monocytogenes–Based Immunotherapy in Patients With NSCLC: Results From Two Phase 1 Studies

“…In the combination study, two treatment-related deaths occurred because of pneumonitis, suggesting that the combination could potentially increase the risk of this toxicity known to be associated with anti–PD-1 or anti–PD-L1 therapies. 30 …”

Inflammatory Markers and Procalcitonin Predict the Outcome of Metastatic Non-Small-Cell-Lung-Cancer Patients Receiving PD-1/PD-L1 Immune-Checkpoint Blockade

“…This work is part of a retrospective real-world evidence (RWE) multi-institutional database study including 95 chemo-refractory mNSCLC patients consecutively enrolled to receive salvage therapy with anti-PD-1 (nivolumab) or anti-PD-L1 (atezolizumab) mAb at the OU-RC, and ROU-SI between September 2015 and April 2020 with a median follow-up time of 28 months (34)(35)(36).…”