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Abstract Immune checkpoints are essential for preventing immunopathology but can also obstruct anti-tumor immune responses. Recent medical advances in blocking these mechanisms have therefore opened promising avenues in the treatment of cancer. Various blocking antibodies targeting the immune checkpoints programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are now approved for human use. This review summarizes the properties of PD-1 and CTLA-4 in physiological and tumor settings, and examines the treatment efficacy, side effects and biomarkers of their inhibitors. Future avenues in the application and development of immune checkpoint inhibitors for the treatment of cancer are also explored.

Abstract A 74-year-old woman noticed an edematous erythema on the right upper eyelid two months before her first medical examination, and slight fever, arthralgia and edematous erythema on the forearms and palms around the time of the first medical examination. She presented with typical skin lesions of dermatomyositis including Gottron’s signs and a heliotrope rash without any abnormal muscle symptoms. An examination by gastrointestinal endoscopy and a computed tomography scan of the chest revealed that she was complicated with stomach cancer (Stage ⅠA), colon cancer　(Stage Ⅰ) and interstitial pneumonia (IP). She was diagnosed with anti-MDA5 antibody-positive clinically amyopathic dermatomyositis (CADM) complicated with two cancers. Because the IP became aggravated, she was treated with corticosteroids at an initial dose of 1 mg/kg/day and immunosuppressive therapies. Tacrolimus was discontinued due to thrombocytopenia, and she also had an allergic reaction to cyclophosphamide. The administration of azathioprine at a dose of 75 mg/day prevented the exacerbation of IP. We were able to be taper the dose of corticosteroids, and endoscopic stomach surgery and abdominal rectal surgery was performed. The anti-MDA5 antibody is a characteristic myositis-specific autoantibody associated with CADM and IP, which may cause a poor prognosis. CADM complicated with malignancy occurs less frequently than similarly complicated dermatomyositis and, to the best of our knowledge, this is the first case of CADM complicated with two cancers.

Abstract A 45-year-old male suffered from persistent swelling and redness, with pain in his left lower leg and ankle. Pathological findings isolated from the ankle joint by arthroscopic synovectomy showed mild synovitis. Initially, this case was diagnosed as chronic mild arthritis and later treated as phlegmon because of the persistent redness and swelling inflammatory findings in his left lower leg. A systemic survey was performed. Based on the findings—such as chronic ankle arthritis with ipsilateral plantar pustulosis, chronic recurrent multifocal osteomyelitis in left distal tibia with MRI, calcaneal osteitis with computed tomography, and pathological findings that neither malignant tumor nor infection was detected—this case reached the definitive diagnosis of SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. The hot spots detected in the bilateral sternoclavicular and costosternal joints with bone scintigraphy and their arthritic change detected by computed tomography also supported the diagnosis of SAPHO syndrome. This case was refractory to NSAIDS; therefore, the TNF inhibitor certolizumab pegol was tried. This agent rapidly improved not only the chief complaints but also the objective symptoms and laboratory findings at most six weeks after its administration.

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Discoid lupus erythematosus (DLE) is an autoimmune disorder that usually occurs on sun exposed areas. We describe a case of a 31-year-old man with reddish-purple, atrophic plaques on the nose and the bilateral cheeks. Histopathologic and direct immuneofluorescent studies confirmed DLE diagnosis. The skin lesion had been previously resistant to topical clobetasol propionate 0.05% and tacrolimus 0.1% since 2012, and were treated with oral hydroxychloroquine (HCQ)  (300 mg daily). Two weeks later, the diarrhea happened frequently as side effects. Then, the dcreased HCQ 200 mg daily improved the diarrhea moderately. The patient who had a history of urticaria also complained about urticarial reaction much more frequently 3 weeks later more than the start, which was improved very much by epinastine (10 mg daily) administration. CLASI (cutaneous lupus erythematsus disease area and severity index) activity score improved from 11 to 5 for 3 months. 

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