It has been a productive summer and fall for the lab, with 3 publications reaching the finish line within the past couple months. All three were thematically linked, exploring how immune cells behave within the complex tumor microenvironment, and how we can better study those behaviors.
Ildefonso Silva-Junior’s study in Communications Biology examines checkpoint blockade from the perspective of the metastatic lymph node microenvironment. Using a mouse model of melanoma lymph node metastasis, Ildefonso found that successful checkpoint blockade was associated with broad remodeling of the lymph node immune environment, including prominent changes in macrophages. The work reinforces an emerging theme in our lab: effective cancer immunotherapy involves not only T-cell activation, but coordinated changes in the surrounding immune and stromal microenvironment. Check out my institution’s press release on the work, as well as my blogpost in Springer Research Communities.
Trinity’s work, published in Frontiers in Oncology, asks what PD-L1 does to macrophages themselves. PD-L1 is best known as a ligand that suppresses PD-1-expressing T cells, but whether PD-L1 also intrinsically regulates macrophage function remains less clear. Using both genetic deletion and antibody blockade, Trinity found that disrupting macrophage PD-L1 did not broadly change conventional macrophage polarization or phagocytosis. Instead, PD-L1 perturbation altered immunoregulatory surface molecules, with a particularly consistent reduction in CD80. The project was apparently simple on its face, but required a lot of careful experimentation and reveals much about the challenging biology of how macrophages interact with the tumor microenvironment.
Finally, Tina and I published a new STAR Protocols article describing our approach for live imaging of immune-cell behavior in mouse tumors. The protocol details how to prepare viable tumor slices using a vibratome and perform time-lapse two-photon microscopy to track fluorescent immune cells. This approach allows researchers to quantify immune-cell migration and cell-cell interactions while preserving the three-dimensional tumor microenvironment, without requiring intravital imaging.
Together, these papers reflect our lab’s broader interest in understanding immunity as something that happens not only within individual immune cells, but through their interactions with one another and with the tissue environments they inhabit.
Congratulations to Ildefonso, Trinity, Tina, and everyone who contributed to these studies!