Weekly Digests

2019

March

An “IF/THEN” CAR T cell that targets only the tumor

March 27, 2019

CD19-targeted CAR T cells can be incredibly effective against B cell malignancies, however, they do not discriminate between malignant and healthy cells. In the case of lineage-restricted CD19, the killing of on-target, off-tumor cells is not a major problem because patients can survive without B cells. A major challenge in treating solid tumor...

Siglec-15 suppresses T cell antitumor response

March 20, 2019

To improve the response rate to cancer immunotherapies, Wang and Sun et al. sought to identify factors beyond the PD-1 axis and other known checkpoint inhibitors that may affect T cell function. Utilizing a high-throughput screening approach as well as in vitro and in vivo studies, the researchers identified Siglec-15 as a suppressor...

NR4A transcription factors control T cell dysfunction programs

March 13, 2019

T cell dysfunction – in the form of exhaustion, anergy, or tolerance – is known to limit the effector functions of T cells, but the molecular mechanisms that induce dysfunctional programs are not fully understood. Two recent studies, published back-to-back in Nature, investigated the mechanisms underlying T cell dysfunction, and through different strategies, both...

TAMs may be friends, not foes, in early-stage tumor T cell response

March 6, 2019

Knowing that immunotherapy that works in mice often fails in patients with solid tumors, and that mouse models mostly utilize tumor cell lines from advanced tumors, Singhal et al. decided to bypass murine studies entirely and instead analyzed the functions of macrophages and monocytes and their interactions with tumor-specific T cells within early-stage...