title: Pneumonitis in cancer patients receiving anti-PD-1 and radiotherapies: Three case reports.
abstract: BACKGROUND
  In development of novel therapies for the treatment of patient with cancer, the use of radiotherapy (RT) can produce significant local control and, in recent studies, has also been shown to mediate anti-tumor responses at distant sites by triggering and enhancing the endogenous cellular immune responses. Although RT induces an abscopal effect in some patients due to enhanced immune response to the tumor, immune-escape mechanisms, including up-regulation of programmed death-ligand 1 (PD-L1) on tumor cells, limit this benefit in other patients. Hence, many studies have promoted the synergy of RT and anti-programmed cell death protein 1 (PD-1) treatment for antitumor immunity. However, outcome may be improved when more therapies are combined, but risk of side effects can be increased.
  
  
  METHODS
  We herein present 3 advanced cancer patients with pulmonary metastasis and who received RT. Later, they underwent anti-PD-1 treatment and unfortunately suffered from anti-PD-1-related pneumonitis over the nonirradiated areas after 4 cycles of treatment. The upregulation of cellular PD-1 expression in these areas was considered and the immune overreaction by anti-PD-1 treatment may cause these severe pulmonary adverse effects.
  
  
  CONCLUSIONS
  Our review of 3 cases warrants careful workup to reduce the risk of side effects by combinative therapy with RT and anti-PD-1 treatment.
authors.affiliation: Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei Division of Hematology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chieh-Sheng
authors.initials: CS
authors.lastname: Lu
authors.forename: Jin-Hwang
authors.initials: JH
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary / Q000628:therapy; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D059248:Chemoradiotherapy; D006801:Humans; D007580:Jejunal Neoplasms / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D008297:Male; D018328:Melanoma, Amelanotic / Q000556:secondary / Q000628:therapy; D008875:Middle Aged; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D000077594:Nivolumab; D011014:Pneumonia / Q000139:chemically induced / Q000209:etiology*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms / Q000473:pathology; D013945:Thymoma / Q000556:secondary / Q000628:therapy; D013953:Thymus Neoplasms / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab