2025
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Unraveling the role of soluble CTLA-4
April 16, 2025
CTLA-4 is a well established immune checkpoint with a key a role in limiting autoimmunity, but it exists in both membrane-bound (mCTLA-4) and soluble (sCTLA-4) forms, and the different sources, kinetics, and functions of sCTLA-4 in particular are not fully understood. In research recently published in Immunity, Osaki and Sakaguchi explored numerous aspects...
KEYSTONE SYMPOSIA: Cancer Immunotherapy: Clinical Lessons to New Modalities
April 9, 2025
The ACIR team attended the Keystone Symposia on Cancer Immunotherapy: Clinical Lessons to New Modalities held on March 16-19, 2025 in Banff, AB, Canada. This week’s extensive special feature covers select talks from the conference. We have organized the content by topics below. (This Keystone Symposia conference is available for On Demand viewing...
Translation dysregulation in cancer produces targetable antigens
April 2, 2025
Dysregulation of translation and protein synthesis is often observed in cancer, but whether this results in the production of targetable antigens has not been fully explored. Investigating this possibility, Weller, Bartok, and McGinnis et al. used CRISPR-Cas9 to study the effects of tRNA wybutosine (yW)-synthesizing protein 2 (TYW2) – a tRNA transferase that...
From TCRs to immunotherapy targets: detection of antigens in pediatric brain tumors
March 26, 2025
Few targetable antigens are known for pediatric brain tumors, which have limited immunotherapy development. Based on this pressing need, Raphael et al. analyzed the TCR repertoires of tumor-infiltrating T cells (TILs), and predicted antigens based on these repertoires. Their results were recently published in Science Translational Medicine. The researchers used bulk transcriptomic data...
Finding the right combination: new insights in anti-PD-1 plus anti-CTLA-4 or anti-LAG3
March 19, 2025
Treatment with checkpoint blockades alone or in various combinations can induce strong antitumor responses, but identifying which treatment or combination will work best for each individual patient is still a challenge. In work recently published in Cancer Cell, Li and Zandberg et al. evaluated results and T cell dynamics from a neoadjuvant trial...
Tumoral RNA splicing: source of neoantigens for off-the-shelf therapies?
March 12, 2025
Immunotherapies targeting tumor-specific antigens (TSAs) derived from somatic mutations have limited potential in tumors with low mutational burdens. A recently discovered source of TSAs are cancer-specific splicing events (neojunctions; NJs), which have the potential to induce CD8+ T cell responses. What remains unknown is whether these NJs are conserved spatially and temporally across...
AACR IO 2025
March 5, 2025
The ACIR team attended the newly established AACR IO meeting held on February 23-26, 2025 in Los Angeles, CA, USA. This week’s extensive special feature covers select talks from the conference. We have organized the content by topics below. Welcome Keynote AddressesJim AllisonArlene Sharpe Neoantigens and ERVsCatherine WuChristopher KlebanoffAlena GrosSebastian AmigorenaGeorge Kassiotis CytokinesChristopher...
TLR agonism and PD-1 blockade unfortunately activate suppressor cells
February 26, 2025
The activation of an immune response involves a system of checks and balances. While immunotherapies can be used to tip the scales, they are not always effective, as resistance mechanisms may act to counter desired responses. In research recently published in Science Translational Medicine, Nishinakamura and Shinya et al. found that a combination...
Neoantigen vaccination shows promising prevention of recurrence of high-risk kidney cancer
February 19, 2025
Kidney cancer is a common cancer type, and about 75-80% of cases are clear cell renal cell carcinoma (RCC). Patients with RCC are often faced with a high risk of cancer recurrence after complete surgical removal. In a recent Phase I clinical trial published in Nature, Braun and colleagues investigated the potential of...
PD-L1 and CD80 interactions make DCs move
February 12, 2025
Research has shown that PD-L1 expression on dendritic cells (DCs) is essential for intracellular signaling that plays a role in chemokine-mediated DC migration. In a recent paper in Science Advances, Kantheti et al. investigated whether the extracellular interaction of PD-L1 on DCs with PD-1 or with CD80 in cis or in trans plays...
Cholesterol supports cDC maturation, while AXL dampens it
February 5, 2025
The maturation of dendritic cells plays a critical role in initiating a cascade of immune responses, but exactly how cDCs mature in the absence of inflammation is not entirely understood. Investigating this process, Belabed and Park et al. found that following the uptake of cellular debris and antigens, cDCs increase transport and synthesis...
First glimpses of efficacy of personalized neoantigen vaccine plus checkpoint blockade in advanced cancers
January 29, 2025
Few patients with advanced cancer respond or have durable response to current immunotherapies. One of the challenges is that neoantigen-specific T cell responses only rarely spontaneously arise in many tumors. Therefore, therapies that trigger the induction of neoantigen-specific T cells, such as vaccination, have the potential to increase the efficacy of immune checkpoint...
Why anti-CTLA-4 promotes better memory responses than anti-PD-1
January 22, 2025
In the clinic, anti-CTLA-4 induces more durable responses than anti-PD-1. In recent research, Mok et al. investigated possible mechanisms underlying this durability by using a variety of mouse tumor and vaccine models. They found that anti-CTLA-4 induced stronger memory responses than anti-PD-1 by preserving CD8+ T cells with high levels of TCF-1 and...
Autologous neoantigen-directed T cell therapy shows promise in clinic
January 15, 2025
While major progress has been made in targeted and immune checkpoint blockade (ICB) therapy for melanoma, many patients do not respond or their response is not durable. To investigate a new approach for these patients, Borgers et al. performed a Phase 1 study assessing targeted adoptive T cell therapy (ACT) directed against patient-specific...
What really happens when you block TIGIT and PD-L1 together
January 8, 2025
Both PD-1 and TIGIT are checkpoint molecules known to inhibit the antitumor effects of CD8+ T cells, and blocking them in combination has been shown to have synergistic immunotherapeutic effects. However, the exact mechanism and dynamics of this synergy are incompletely understood. In recent research, Nutsch, Banta, and Wu et al. utilized a...
