Lessons for the Next Generation of Scientists from the Second Annual Arthur and Sandra Irving Cancer Immunology Symposium.

The Arthur and Sandra Irving Cancer Immunology Symposium has been created as a platform for established cancer immunologists to mentor trainees and young investigators as they launch their research career in the field. By sharing their different paths to success, the senior faculty mentors provide an invaluable resource to support the development of the next generation of leaders in the cancer immunology community. This Commentary describes some of the key topics that were discussed during the 2022 symposium: scientific and career trajectory, leadership, mentoring, collaborations, and publishing.

Constitutive Interferon Attenuates RIPK1/3-Mediated Cytokine Translation.

Receptor-interacting protein kinase 1 (RIPK1) and 3 (RIPK3) are well known for their capacity to drive necroptosis via mixed-lineage kinase-like domain (MLKL). Recently, RIPK1/3 kinase activity has been shown to drive inflammation via activation of MAPK signaling. However, the regulatory mechanisms underlying this kinase-dependent cytokine production remain poorly understood.

Liquid Exfibration and Optoelectronic Devices of Fibrous Phosphorus.

Quasi-one-dimensional (Q1D) semiconductor materials, such as carbon nanotubes, SbSI, MP (M = Li, Na, K), and selenium and tellurium nanowires, show amazing potential for applications in future nanoelectronic and optoelectronic devices. However, intricate chirality in the structure of carbon nanotubes limits their applications. Also, the performance of MP in optoelectronics has yet to be extensively explored.

Proteomics-based screening of the target proteins associated with antidepressant-like effect and mechanism of Saikosaponin A.

Depression is a commonly occurring neuropsychiatric disease with an increasing incidence rate. Saikosaponin A (SA), a major bioactive component extracted from Radix Bupleuri, possesses anti-malignant cell proliferation, anti-inflammation, anti-oxidation and liver protective effects. However, few studies have investigated SA's antidepressant effects and pharmacological mechanisms of action.

Enhanced Performance of a CVD MoS Photodetector by Chemical in Situ n-Type Doping.

Transition metal dichalcogenides (TMDs) are a category of promising two-dimensional (2D) materials for the optoelectronic devices, and their unique characteristics include tunable band gap, nondangling bonds as well as compatibility to large-scale fabrication, for instance, chemical vapor deposition (CVD). MoS is one of the first TMDs that is well studied in the photodetection area widely. However, the low photoresponse restricts its applications in photodetectors unless the device is applied with ultrahigh source-drain voltage ( V) and gate voltage ( V).

Graphene/Si Schottky solar cells: a review of recent advances and prospects.

Graphene has attracted tremendous interest due to its unique physical and chemical properties. The atomic thickness, high carrier mobility and transparency make graphene an ideal electrode material which can be applied to various optoelectronic devices such as solar cells, light-emitting diodes and photodetectors. In recent years, there has been a growing interest in developing graphene/silicon Schottky junction solar cells and the power conversion efficiency has reached up to 15.

Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during infection.

Cell death and inflammation are intimately linked during infection. Pathogenic inhibits the MAP kinase TGFβ-activated kinase 1 (TAK1) via the effector YopJ, thereby silencing cytokine expression while activating caspase-8-mediated cell death. Here, using in corroboration with costimulation of lipopolysaccharide and (5Z)-7-Oxozeaenol, a small-molecule inhibitor of TAK1, we show that caspase-8 activation during TAK1 inhibition results in cleavage of both gasdermin D (GSDMD) and gasdermin E (GSDME) in murine macrophages, resulting in pyroptosis.

Host-Intrinsic Interferon Status in Infection and Immunity.

Most genetic ablations of interferon (IFN) signaling abolish both the experimentally induced IFN response and constitutive IFN, whose effects are well established in autoimmunity but understudied during infection. In host-pathogen interactions, most IFN-mediated responses are attributed to infection-driven IFN. However, IFNs confer their activity by regulating networks of interferon-stimulated genes (ISGs), a process that requires de novo transcription and translation of both IFN and downstream ISGs through feedback of IFN receptor signaling.

Constitutive Interferon Maintains GBP Expression Required for Release of Bacterial Components Upstream of Pyroptosis and Anti-DNA Responses.

Legionella pneumophila elicits caspase-11-driven macrophage pyroptosis through guanylate-binding proteins (GBPs) encoded on chromosome 3. It has been proposed that microbe-driven IFN upregulates GBPs to facilitate pathogen vacuole rupture and bacteriolysis preceding caspase-11 activation. We show here that macrophage death occurred independently of microbial-induced IFN signaling and that GBPs are dispensable for pathogen vacuole rupture.

Constitutive interferon signaling maintains critical threshold of MLKL expression to license necroptosis.

Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein.

Cutting Edge: Novel Tmem173 Allele Reveals Importance of STING N Terminus in Trafficking and Type I IFN Production.

With the stimulator of IFN genes (STING) C terminus being extensively studied, the role of the N-terminal domain (NTD) of STING remains an important subject of investigation. In this article, we identify novel mutations in NTD of Sting of the MOLF strain in response to HSV and Listeria monocytogenes both in vitro and in vivo. These mutations are responsible for low levels of IFN-β caused by failure of MOLF STING to translocate from the endoplasmic reticulum.

CD209a expression on dendritic cells is critical for the development of pathogenic Th17 cell responses in murine schistosomiasis.

In murine schistosomiasis, immunopathology and cytokine production in response to parasite eggs are uneven and strain dependent. CBA/J (CBA) mice develop severe hepatic granulomatous inflammation associated with prominent Th17 cell responses driven by dendritic cell (DC)-derived IL-1β and IL-23. Such Th17 cells fail to develop in low-pathology C57BL/6 (BL/6) mice, and the reasons for these strain-specific differences in APC reactivity to eggs remain unclear.

The N terminus of SKAP55 enables T cell adhesion to TCR and integrin ligands via distinct mechanisms.

The T cell receptor (TCR) triggers the assembly of "SLP-76 microclusters," which mediate signals required for T cell activation. In addition to regulating integrin activation, we show that Src kinase-associated phosphoprotein of 55 kD (SKAP55) is required for microcluster persistence and movement, junctional stabilization, and integrin-independent adhesion via the TCR. These functions require the dimerization of SKAP55 and its interaction with the adaptor adhesion and degranulation-promoting adaptor protein (ADAP).