Cancer-induced immune responses affect tumor progression and therapeutic response. In multiple murine models and clinical datasets, we identified large variations of neutrophils and macrophages, which define “immune subtypes” of triple negative breast cancer (TNBC) including neutrophil-enriched (NES) and macrophage-enriched subtypes (MES). Different tumor-intrinsic pathways and mutual regulation between macrophages/monocytes and neutrophils contribute to the development of dichotomous myeloid compartment. MES contains predominantly macrophages that are CCR2-dependent and exhibit variable responses to immune checkpoint blockade (ICB). NES exhibits systemic and local accumulation of immunosuppressive neutrophils (or granulocytic myeloid-derived suppressor cells (gMDSCs), is resistant to ICB, and contains a minority of macrophages that appear to be unaffected by CCR2 knockout. A MES-to-NES conversion mediated acquired ICB resistance of initially sensitive MES models. Our results demonstrate diverse myeloid cell frequencies, functionality, and potential roles in immunotherapies, and highlight the need to better understand the inter-patient heterogeneity of the myeloid compartment.

Acute fibrinous organising pneumonia is distinct from the classic diffuse alveolar damage, organising pneumonia and eosinophilic pneumonia. A 52-year-old woman presented with fever, productive cough, night sweats and left-sided pleuritic chest pain for a week. Physical examination was significant only for decreased breath sounds in the left infraclavicular area laterally. Imaging studies revealed a peripheral thick-walled left upper lobe cavitary lesion, left lower lobe consolidation and an enlarged subcarinal lymph node. She was treated with doxycycline for 10 days without improvement. Pertinent laboratory tests, microbiologic workup and fibre-optic bronchoscopy were non-diagnostic and a CT-guided left upper lobe lung biopsy revealed acute fibrinous organising pneumonia. She was treated with azithromycin with complete resolution of symptoms. To our knowledge, this is the first reported case of acute fibrinous organising pneumonia presenting as a cavitary lung lesion and the first with treatment response to azithromycin.

No abstract

Dabigatran, a new oral anticoagulant, is a direct thrombin inhibitor used as an alternative to warfarin to reduce the risk of stroke and systemic embolism with nonvalvular atrial fibrillation. We report a case of a man who resumed dabigatran after 6 weeks of prior therapy and began experiencing hematuria with worsening kidney function. Renal biopsy with immunofluorescence and electron microscopy showed mesangial deposits consistent with immunoglobulin A nephropathy. With discontinuation of dabigatran and addition of methylprednisolone, the gross hematuria cleared and urine output improved.