PD-1 inhibition in malignant melanoma and lack of clinical response in chronic lymphocytic leukemia in the same patients: a case series.

Chronic lymphocytic leukemia (cll) is the most common adult leukemia in the Western world. Unfortunately, affected patients are often immunosuppressed and at increased risk of infection and secondary malignancy. Previous meta-analysis has found that patients with cll have a risk of melanoma that is increased by a factor of 4 compared with the general population. Recent advances in the understanding of the PD receptor pathway have led to immunotherapies that target cancer cells. The use of PD-1 inhibitors is now considered first-line treatment for BRAF wild-type metastatic melanoma. Interestingly, early preclinical data suggest that inhibition of that pathway could also be used in the treatment of cll; however, recent clinical data did not support the effectiveness of that approach. In this case series, we highlight 2 cases in which patients with cll and concurrent malignant melanoma underwent treatment with PD-1 inhibitors and were found to experience reductions in their white blood cell counts without improvement in their hemoglobin. Those cases further illustrate that treatment of cll with PD-1 inhibitors is ineffective.

Follicular dendritic cell secreted protein FDC-SP controls IgA production.

Follicular dendritic cell secreted protein (FDC-SP) is a secreted peptide predominantly expressed in mucosal tissues. We previously reported that FDC-SP transgenic mice have altered B-cell responses to systemic immunization; however, the role of FDC-SP in mucosal immunity is unknown. Here, we report that FDC-SP functions in regulating immunoglobulin A production. FDC-SP transgenic mice show decreased IgA levels in serum, saliva, and bronchoalveolar lavage fluid. Reciprocally, FDC-SP-deficient mice show significantly increased IgA levels in serum and intestinal lavage, associated with accumulation of IgA+ cells in blood, bone marrow, Peyer's patches, and lymph nodes. FDC-SP-deficient mice generated higher titers of antigen-specific IgA but normal IgG1 responses upon immunization. Purified FDC-SP transgenic B cells generated decreased IgA responses to transforming growth factor ß (TGFß)+interleukin 5 (IL5) stimulation. Consistent with a direct effect of FDC-SP on B cells, recombinant FDC-SP suppressed B-cell IgA production in vitro. Six- to 14-month-old FDC-SP-deficient mice show IgA deposition in kidney glomeruli, which was associated with proteinuria and pathology consistent with mild IgA nephropathy (IgAN). Our results demonstrate a novel biological activity of FDC-SP in controlling B-cell IgA production and identify FDC-SP-deficient mice as a novel mouse model of IgAN.