Six simple tips to help ensure progress during your Ph.D. studies.
Effector function allows antibodies to communicate with a large portion of the immune system. Now, it looks like anti-CTLA4 antibodies can also take advantage of this, but depleting regulatory T cells. Effector signaling is complicated and important enough there is surely much engineering still to be done.
These results are remarkable: Warfarin (an accidental TAM inhibitor) reduces incidence of cancer by ~20% in patients >50. These new results complement some of the less definitive results of earlier studies.
An interesting paper on the relationship between the development of tolerance and resistance. It’s in bacteria but surely has direct ties to selectively toxic drugs in cancer as well. They show that tolerance can directly enable rare, resistance-causing mutations to develop. They also come up with an explanation for why tolerance would develop before resistance—the routes to tolerance are by many different mutational changes, while resistance had a more restrictive set of routes.
This work shows that in addition to being a tumor cell-intrinsic resistance factor to ionizing radiation, AXL signaling drives decreased MHC-I abundance and immunosuppressive cytokine expression. The AXL-proximal signaling that drives this effect is not worked out—it would be interesting to know what signaling is involved to determine how specific this is to TAM receptors vs. other kinases.
An interesting paper from a few hospitals, mainly in Boston. They’re doing targeted capture and sequencing of a broad panel of patients to try and design therapies around that data. They find focal amplification of AXL in ~1% of patients. AXL inhibitor was tried in one of those patients and gave a striking response.
A really interesting study on how IGF1 acts as a signal from macrophages to redirect efferocytosis toward immune cells. The redirection works even with phosphatidylserine vesicles, and prevents inflammation after an allergy challenge.
Cummings et al created an experimental model in which they could selectively induce apoptosis in a subpopulation of cells, which then allowed them to look at the response within the surrounding cells. Apoptotic cell debris leads to an immunosuppressive response in a variety of cell types, though with important differences as well.
Practical advice for how to best present scientific data. As stated in the article, “a more accurate definition for scientific visualization would be a graphical interface between people and data.”
We frequently are asked about the use of warfarin in cancer patients and whether it is linked to survival. This is a list of a few studies found in the literature.
A first, classic model of Fc receptor activation.