TY - JOUR T1 - Progressive hypoventilation due to mixed CD8<sup>+</sup> and CD4<sup>+</sup> lymphocytic polymyositis following tremelimumab - durvalumab treatment JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/s40425-017-0258-x VL - 5 IS - 1 SP - 54 AU - Sooraj John AU - Scott J. Antonia AU - Trevor A. Rose AU - Robert P. Seifert AU - Barbara A. Centeno AU - Aaron S. Wagner AU - Ben C. Creelan Y1 - 2017/12/01 UR - http://jitc.bmj.com/content/5/1/54.abstract N2 - Background The combination of CTLA-4 and PD-L1 inhibitors has a manageable adverse effect profile, although rare immune-related adverse events (irAE) can occur.Case presentation We describe an autoimmune polymyositis following a partial response to combination tremelimumab and durvalumab for the treatment of recurrent lung adenocarcinoma. Radiography revealed significant reduction in all metastases; however, the patient developed progressive neuromuscular hypoventilation due to lymphocytic destruction of the diaphragmatic musculature. Serologic testing revealed a low level of de novo circulating antibodies against striated muscle fiber. Immunohistochemistry revealed type II muscle fiber atrophy with a mixed CD8+ and CD4+ lymphocyte infiltrate, indicative of inflammatory myopathy.Conclusions This case supports the hypothesis that muscle tissue is a target for lymphocytic infiltration in immune checkpoint inhibitor-associated polymyositis. Further insights into the autoimmune mechanism of PM will hopefully contribute to the prevention and treatment of this phenomenon.Abbreviations:AChRAcetylcholine receptorASMAnti-striated muscleBiPAPBilevel positive airway pressureCDCluster of differentiationCO2Carbon dioxide levelCSFCerebrospinal fluidCTComputed tomographyCTCAECommon toxicity criteria for adverse eventsCTLA-4Cytotoxic T-lymphocyte-associated protein 4GvHDGraft-versus-host diseaseH&amp;EHematoxylin and eosinHIERHigh pH heat induced epitope retrievalICH –GCPInternational conference on harmonization good clinical practiceIFN-γInterferon gammaIHCImmunohistochemistryirAEImmune-related adverse eventsIVIntravenousIVIGIntravenous immunoglobulin GKRASKirsten rat sarcoma viral oncogene homologMHCMajor histocompatibilityMRIMagnetic resonance imagingMuSKMuscle specific kinase proteinNCTNational clinical trialsPBMCsPeripheral blood mononuclear cellsPD-1Programmed cell death protein 1PD-L1Programmed death ligand 1PexPlasma exchangePMPolymyositisRECISTResponse evaluation criteria in solid tumorTAR DP-43Transactive response DNA binding protein 43 kDaTCRT cell receptorVGCCVoltage gated calcium channelwksWeeks ER -