Weekly Digests

2019

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Potassium determines the fate of T cells

April 17, 2019

In a paper recently published in and featured on the cover of Science, Vodnala and Eil et al. investigated why some patients have dysfunctional tumor-infiltrating lymphocytes (TILs), while others have T cells that behave like stem cells in their capacity to self-renew, proliferate, and destroy large tumors. They found that this difference is...

AACR Annual Meeting 2019

April 10, 2019

Last week, the ACIR team attended the AACR Annual Meeting 2019 in Atlanta, Georgia. This week’s extensive special feature covers select talks from the conference. We have organized the content by topics below. T cells in Immune surveillance, Exhaustion, and TherapiesEmerging Immunotherapy ApproachesTME and Tumor EscapeClinical Trials T cells in Immune surveillance, Exhaustion...

Targeting macrophages and neutrophils enhances response to chemotherapy

April 3, 2019

Previous research has shown that the immune system contributes to chemotherapy response; therefore, immunosuppressive mechanisms can be hypothesized to limit the cytotoxic effect. In a study recently published in Nature Cell Biology, Salvagno et al. demonstrated that targeting immunosuppressive macrophages and neutrophils enhances the efficacy of platinum-based chemotherapy in a mouse breast cancer...

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...

Boosting immunity with the microbiome

February 27, 2019

In recent years, the microbiome has gained increased attention for its effects on the immune system, and it is well known to influence the CD4+ T cell compartment; however, little is known of its effect on CD8+ T cells. In a study recently published in Nature, Tanoue and Morita et al. show that...

Found: tumor-reactive regulatory T cells

February 20, 2019

Elevated levels of CD4+ regulatory T cells (Tregs) are often found in human tumors and are associated with poor prognosis. However, the antigen specificity of intratumoral Tregs is not well understood. In a paper recently published in Science Immunology, Ahmadzadeh et al. analyzed the relationships of TCR sequences between intratumoral FOXP3+ Tregs, circulating...

Tcf1+ progenitor-like T cell subsets sustain antitumor responses

February 13, 2019

Two articles, recently published back to back in Cell, identify important roles for T cells expressing Tcf1 (encoded by Tcf7), a transcription factor known to play roles in maintaining a relatively undifferentiated T cell state, promoting self-renewal and T cell memory. Kurtulus and Madi et al., working primarily with the MC38-OVA colon carcinoma...

Koch Institute Immune Engineering Symposium 2019

February 6, 2019

Last week, the ACIR team attended the Koch Institute Immune Engineering Symposium in Cambridge, Massachusetts. This week’s extensive special feature covers select talks from the conference. Robert Schreiber opened the symposium by examining the role of MHC II and CD4+ T cells in tumor control, particularly with the backdrop that many tumors do...

Dysfunction: what’s in a name?

January 30, 2019

To gain insight into the mechanisms underlying response and resistance to immunotherapy, Li, van der Leun, Yofe, and Lubling et al. set out to molecularly characterize the expressed gene sets of tumor-infiltrating immune cells in order to quantitatively and qualitatively analyze the heterogeneity within and between cancer patients. The results were recently published...

Communication is key in PD-1 blockade

January 23, 2019

The efficacy of immunotherapy is dependent on a variety of factors and cells in the tumor microenvironment, and understanding these complex interactions is critical to understanding and improving the efficacy of treatment. To study some of these interactions, Garris and Arlauckas et al. used real-time intravital imaging, RNA sequencing, and a series of...

NKG2A blockade releases the brakes on CD8+ T cells and NK cells

January 16, 2019

With the success of immune checkpoint blockade in some cancer patients, but failure in many others, scientists are always on the lookout for new checkpoints to target. The inhibitory receptor NKG2A is found on many NK cells and few CD8+ T cells in peripheral blood. It heterodimerizes with CD94 and, upon binding its...

The shape of intratumor heterogeneity

January 9, 2019

Most tumors exhibit a high degree of genetic and functional heterogeneity, but how that heterogeneity is established and evolves in situ under immune pressure has been difficult to study. To tackle this obstacle, Milo et al. established a mouse model of MYC-driven B cell lymphoma with a large degree of genetic diversity, both...