Th1 cells are critical tissue organizers of myeloid-rich perivascular activation niches.

Unlabelled: Aggregating immune cells within perivascular niches (PVN) can regulate tissue immunity in infection, autoimmunity and cancer. How cells are assembled at PVNs and the activation signals imparted within remain unclear. Here, we integrate dynamic time-resolved imaging with a novel spatially-resolved platform for microanatomical interrogation of transcriptome, immune phenotype and inflammatory mediators in skin PVNs.

Multiphoton fluorescence microscopy for in vivo imaging.

Multiphoton fluorescence microscopy (MPFM) has been a game-changer for optical imaging, particularly for studying biological tissues deep within living organisms. MPFM overcomes the strong scattering of light in heterogeneous tissue by utilizing nonlinear excitation that confines fluorescence emission mostly to the microscope focal volume. This enables high-resolution imaging deep within intact tissue and has opened new avenues for structural and functional studies.

T cells use focal adhesions to pull themselves through confined environments.

Immune cells are highly dynamic and able to migrate through environments with diverse biochemical and mechanical compositions. Their migration has classically been defined as amoeboid under the assumption that it is integrin independent. Here, we show that activated primary Th1 T cells require both confinement and extracellular matrix proteins to migrate efficiently.

T cells Use Focal Adhesions to Pull Themselves Through Confined Environments.

Immune cells are highly dynamic and able to migrate through environments with diverse biochemical and mechanical composition. Their migration has classically been defined as amoeboid under the assumption that it is integrin-independent. Here we show that activated primary Th1 T cells require both confinement and extracellular matrix protein to migrate efficiently.

Ccr2+ Monocyte-Derived Macrophages Influence Trajectories of Acquired Therapy Resistance in Braf-Mutant Melanoma.

Unlabelled: Therapies targeting oncogene addiction have had a tremendous impact on tumor growth and patient outcome, but drug resistance continues to be problematic. One approach to deal with the challenge of resistance entails extending anticancer treatments beyond targeting cancer cells by additionally altering the tumor microenvironment. Understanding how the tumor microenvironment contributes to the evolution of diverse resistance pathways could aid in the design of sequential treatments that can elicit and take advantage of a predictable resistance trajectory.