License for a CAR T: Examining patient eligibility.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape of lymphoma and is now approved by the FDA for multiple indications. Given that the indications for CAR T-cell therapy are expanding, a larger patient population will be eligible to receive this treatment in the coming years. Pivotal clinical trials leading to FDA approval of CAR T-cell products required patients to have adequate organ function and good performance status.

A real-world study of pneumonitis in non-small cell lung cancer patients receiving durvalumab following concurrent chemoradiation.

Background: Locally advanced non-small cell lung cancer (LA-NSCLC) treated with the programmed death-ligand 1 inhibitor durvalumab has been associated with significant rates of pneumonitis, which has led to higher rates of discontinuation of therapy in real-world populations. Thus far there has been no consensus in the literature on the impact of pneumonitis on survival.

Methods: This is a retrospective cohort study of veterans receiving durvalumab between 12/5/2017 and 4/15/2020.

Leucocytosis and Stroke in a Lung Cancer Patient.

Unlabelled: Significant leucocytosis in the setting of an underlying malignancy may be attributed to several causes and is not uncommon; however, extreme leucocytosis (>50×10 cells/l) and hypereosinophilia is less common and may represent a paraneoplastic syndrome. The underlying mechanism is thought to be bone marrow stimulation by tumour-produced cytokines, most notably interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF). This paraneoplastic syndrome is likely reflective of extensive disease and dissemination, and options for treatment are limited but include tumour resection, corticosteroids and hydroxyurea.

The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression.

We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4 T cells and CD8 T-cell activation.

NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA.

Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance.

The progression of pancreatic oncogenesis requires immune-suppressive inflammation in cooperation with oncogenic mutations. However, the drivers of intratumoral immune tolerance are uncertain. Dectin 1 is an innate immune receptor crucial for anti-fungal immunity, but its role in sterile inflammation and oncogenesis has not been well defined.

γδ T Cells Support Pancreatic Oncogenesis by Restraining αβ T Cell Activation.

Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated γδT cell population, which constituted ∼40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of γδT cells was contingent on diverse chemokine signals.