Context.— Delta-like protein 3 (DLL3) is a protein that is implicated in the Notch pathway. Objective.— To present data on DLL3 prevalence in small cell lung cancer and staining characteristics of the VENTANA DLL3 (SP347) Assay. In addition, the assay's immunoreactivity with other neoplastic and nonneoplastic tissues is outlined. Design.— Individual formalin-fixed, paraffin-embedded specimens of small cell lung cancer and tissue microarrays comprising neoplastic and nonneoplastic tissues were procured. Sections were cut and stained with DLL3 (SP347) assay. The slides were examined to determine prevalence, staining characteristics, and immunoreactivity. Results.— Cytoplasmic and/or membranous staining was observed in 1040 of 1362 specimens of small cell lung cancer (76.4%). Homogenous and/or heterogeneous and partial and/or circumferential granular staining with varied intensities was noted. Immunoreactivity was also observed in other neoplastic and nonneoplastic tissues. Conclusions.— Our study findings provided the profile of DLL3 staining characteristics that can be used for determining the level of DLL3 expression in small cell lung cancer.

Background Inflammatory bowel disease (IBD) is a multifactorial disorder, with the innate and adaptive immune cells contributing to disease initiation and progression. However, the intricate cross-talk between immune cell lineages remains incompletely understood. The role of CD8+ T cells in IBD pathogenesis has been understudied, largely due to the lack of appropriate models. Methods We previously reported spontaneous colitis in mice with impaired TGFβ signaling due to dendritic cell–specific knockout of TGFbR2 (TGFβR2ΔDC). Here, we demonstrate that crossing TGFβR2ΔDC mice with a Rag1-/- background eliminates all symptoms of colitis and that adoptive transfer of unfractionated CD3+ splenocytes is sufficient to induce progressive colitis in Rag1-/-TGFβR2ΔDC mice. Results Both CD4+ and CD8+ T cells are required for the induction of colitis accompanied by activation of both T-cell lineages and DCs, increased expression of mucosal IFNγ, TNFα, IL6, IL1β, and IL12, and decreased frequencies of CD4+FoxP3+ regulatory T cells. Development of colitis required CD40L expression in CD4+ T cells, and the disease was partially ameliorated by IFNγ neutralization. Conclusions This novel model provides an important tool for studying IBD pathogenesis, in particular the complex interactions among innate and adaptive immune cells in a controlled fashion, and represents a valuable tool for preclinical evaluation of novel therapeutics.

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Background: Immune checkpoint inhibitors (CPIs) are now an accepted standard of care along the treatment algorithm for advanced non-small cell lung cancer (NSCLC). PD-L1 expression using 22C3 immunohistochemistry (IHC) help determine the line of therapy in which CPI are used. Previous studies demonstrated that PD-L1 expression is comparable on cytology versus solid biopsy/histology specimens. We assess the clinical outcomes between patients with PD-L1 expression 50% (high positive) tested using cytology versus histology specimens. Method: This retrospective cohort study includes specimens processed between . Patients were included in the study if they were seen by a medical oncologist for consideration of systemic treatment for advanced NSCLC. Clinical characteristics were extracted from electronic medical records. Overall survival (OS) was defined as time from diagnosis of advanced NSCLC to death and compared by method of PD-L1 analysis (cytology versus histology), adjusting for age, ECOG, weight loss, and receipt of palliative intent radiotherapy, targeted therapy, and CPI. Result: 148 (30.8%) of 481 samples tested 50% for PD-L1 expression. Amongst those, 32 and 37 patients fulfilled eligibility criteria with cytology and histology samples respectively. Baseline characteristics of the two groups are comparable in age, gender, ECOG, histological subtype, and receipt of CPIs. The cytology group had a significantly higher number of patients with baseline pleural effusion (10 vs 4 patients, p¼0.035) and receipt of any systemic therapy (28 vs 22 patients, p¼0.009). The histology group received more palliative intent radiation (24 vs 13, p¼0.044). There was no difference in OS between the cytology and histology groups. Median OS in the cytology group was 11.9 versus 8.0 months in the histology group; adjusted HR 0.98 (95% CI 0.43-2.26). Amongst patients who received systemic therapy, survival was longer if patients were exposed to CPI during their course of treatment regardless of cytology or histology groups; adjusted HR 0.45 (95% CI 0.22 e 0.90). Conclusion: In advanced NSCLC, CPI treatment guided by specimens analyzed by cytology versus histology were equivalent in survival. Regardless of sample source, patients exposed to CPI in any line of therapy had significantly longer survival than patients without exposure to CPI amongst patients testing high positive for PD-L1. Ongoing analyses are comparing clinical outcomes in patients with other expressions of PD-L1.Background: Fine needle aspirations (FNA) are a common type of sample that is obtained for diagnostic purposes in small cell lung cancer (SCLC) patients due to its relatively less invasive nature. Several delta-like protein 3 (DLL3) therapies that target DLL3 in SCLC are under development. We recently developed an immunohistochemistry assay utilizing a rabbit monoclonal antibody that can be used to identify patients that may potentially respond to DLL3 targeted therapies. Due to the high prevalence of FNA samples in SCLC, the robustness of the VENTANA DLL3 (...