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Purpose: Immune-checkpoint inhibitors have shown therapeutic efficacy in various malignant diseases. However, antiprogrammed death (PD)-1 therapy has not shown clinical efficacy in multiple myeloma.Experimental Design: Bone marrow (BM) mononuclear cells were obtained from 77 newly diagnosed multiple myeloma patients. We examined the expression of immune-checkpoint receptors in BM CD8 þ T cells and their functional restoration by ex vivo treatment with anti-PD-1 and TGFb inhibitors.Results: We confirmed the upregulation of PD-1 and PD-L1 expression in CD8 þ T cells and myeloma cells, respectively, from the BM of multiple myeloma patients. PD-1-expressing CD8 þ T cells from the BM of multiple myeloma patients coexpressed other checkpoint inhibitory receptors and exhibited a terminally dif-ferentiated phenotype. These results were also observed in BM CD8 þ T cells specific to myeloma antigens NY-ESO-1 and HM1.24. BM CD8 þ T cells from multiple myeloma patients exhibited reduced proliferation and cytokine production upon T-cell receptor stimulation. However, anti-PD-1 did not increase the proliferation of BM CD8 þ T cells from multiple myeloma patients, indicating that T-cell exhaustion in multiple myeloma is hardly reversed by PD-1 blockade alone. Intriguingly, anti-PD-1 significantly increased the proliferation of BM CD8 þ T cells from multiple myeloma patients in the presence of inhibitors of TGFb, which was overexpressed by myeloma cells.Conclusions: Our findings indicate that combined blockade of PD-1 and TGFb may be useful for the treatment of multiple myeloma.

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To determine the approximate incidence and clinical features of pernicious anemia in a Korean population, we retrospectively analyzed clinical data for patients with pernicious anemia who were diagnosed between 1995 and 2010 at five hospitals in Chungnam province. Ninety-seven patients were enrolled, who accounted for 24% of patients with vitamin B12 deficiency anemia. The approximate annual incidence of pernicious anemia was 0.3 per 100,000. The median age was 66 (range, 32-98) yr, and the male/female ratio was 1.25. Anemia-associated discomfort was the most common symptom (79.4%), followed by gastrointestinal and neurological symptoms (78.4% and 38.1%, respectively). Pancytopenia was found in 36 patients (37.1%), and autoimmune disorders were found in 15 patients (15.5%). Antibody to intrinsic factor was detected in 62 (77.5%) of 80 patients examined, and antibody to parietal cells was detected in 35 (43.2%) of 81 patients examined. Of the 34 patients who underwent tests for Helicobacter pylori, 7 (12.5%) were positive. The anemia-associated and gastrointestinal symptoms resolved completely in all patients after intramuscular injection of cobalamin, whereas neurological symptoms remained in some. In conclusion, pernicious anemia is less frequent in Koreans than in Western populations; however, the clinical features of this disorder in Koreans do not differ from those of Western cases.

Sunitinib is a small molecular inhibitor of tyrosine kinases and is used to treat advanced renal cell carcinoma and gastrointestinal stromal tumour after disease progression or intolerance to imatinib therapy. Here, we describe biochemical and pathological response of prostate cancer in a patient with metastatic renal cell carcinoma during sunitinib treatment. A 62-year-old man was referred to our hospital because of a mass in the scalp. He was diagnosed with left renal cell carcinoma with right renal and scalp metastases. In addition, synchronous prostate cancer involving less than one-half of the right lobe was found with a prostate-specific antigen (PSA) value of 23.4 ng/ml. Treatment was begun with sunitinib (50 mg daily, 4 weeks on and 2 weeks off). Regarding the prostate cancer, active monitoring was planned considering the far advanced renal cell carcinoma. Surprisingly, the PSA level was 3.4 ng/ml at week 6 and 0.2 ng/ml at week 12, and it subsequently remained normal. At the time of writing (cycle 6 of sunitinib therapy), the prostate nodule significantly decreased in size. Furthermore, a 12-core re-biopsy revealed pathological evidence of regression with sunitinib treatment, with control of his renal cell carcinoma.