2026
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Intratumoral anti-CTLA-4 could reduce severe AEs: Results from a phase 1b clinical trial
May 13, 2026
The combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4), both administered intravenously, has been approved for the treatment of cancer in a variety of settings since 2015, but its use is frequently hindered by severe adverse events, more often associated with the use of anti-CTLA-4. In an effort to reduce this toxicity, Tselikas and...
NK cells unleashed by Treg ablation
May 6, 2026
When tumors lose expression of MHC-I under the selective pressure of CD8+ T cells, NK cells may step in and take on a more prominent antitumor role, but often this is still insufficient to control tumors. Investigating potential mechanisms limiting NK cell antitumor activity, Zhang et al. found that Tregs have a strong...
No cDC1, no worries: cDC2 and cross-dressing prime T cells in response to mRNA-LNP vaccination
April 29, 2026
cDC1s play essential roles in CD8+ T cell priming in response to protein- and DNA-based vaccination. However, whether mRNA vaccines function via a similar mechanism remains unknown. In a recent Nature publication, Jo et al. uncovered the mechanisms of CD8+ T cell priming induced by mRNA-LNP vaccines. The researchers began by assessing OT-I...
Agonist anti-CD40 converts Tregs from foes to friends
April 22, 2026
Recent investigations into the use of agonist anti-CD40 for cancer immunotherapy have shown that this treatment not only enhances APC functions, but also reduces regulatory T cells (Tregs) within the tumor microenvironment (TME), despite a lack of CD40 on these cells. Exploring the mechanism by which this occurs, and whether it might contribute...
Stopping the shredder to unlock a novel source of valuable neoantigens
April 15, 2026
Inadequate neoantigen presentation in cancer hampers the endogenous antitumor immune response and the efficacy of immunotherapy. One mechanism that limits the production of immune-targetable antigens is nonsense-mediated mRNA decay (NMD). NMD degrades transcripts with premature termination codons (PTCs), eliminating a potential source of frameshift antigens, which may serve as an immune-evasion mechanism in...
KEYSTONE SYMPOSIA: Cancer Immunotherapy: Basic Mechanisms Informing Clinical Application
April 8, 2026
The ACIR team attended the Keystone Symposia on Cancer Immunotherapy: Basic Mechanisms Informing Clinical Application held on March 15-18, 2026 in Quebec, QC, 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...
LNP mRNA delivery gets a metabolic boost from amino acid supplement
April 1, 2026
Notice: The article we intended to feature this week was briefly delayed in publication. We will share it with you as soon as the embargo is lifted. In the meantime, we encourage you to revisit last week's feature — it's well worth a read. If you've already read it, skip to the bottom of the...
LNP mRNA delivery gets a metabolic boost from amino acid supplement
March 25, 2026
Lipid nanoparticles (LNPs) have allowed for the delivery of therapeutic mRNA for various therapeutic applications. However, in vivo delivery efficacy is often limited, and research is focused on optimization of LNP formulations. In recent work published in Science Translational Medicine, Chen, Wang, et al. assessed how the in vivo metabolic state impacts LNP...
The surprising effect of TOX in CD4+ T cells
March 18, 2026
In settings of chronic antigen stimulation, such as chronic infection and cancer, expression of the transcription factor TOX in CD8+ T cells has been associated with cell persistence and survival, but also with exhaustion, dysfunction, and poor prognosis. As the role of TOX in CD4+ T cells is less well understood, Naizir et...
Neoantigen vaccination boosts long-lasting T cell responses in TNBC
March 11, 2026
Triple-negative breast cancer (TNBC) is characterized by DNA repair deficiency, genomic instability, and an immunogenic tumor microenvironment, suggesting it might serve as a candidate for individualized vaccination targeting somatic tumor mutation-associated neoantigens. Sahin, Schmidt, et al. recently published the results of a first-in-human clinical study with this strategy in Nature. To develop the...
AACR IO 2026
March 4, 2026
The ACIR team attended the AACR IO meeting held on February 18-21, 2026 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. T cellsPhilip D. GreenbergRafi AhmedFred RamsdellAlexander MarsonRobert G. NewmanOwen N. Witte Checkpoint blockadeFathia Mami-ChouaiDario A. VignaliMegan...
Flt3L fuels DCs to promote ICB-responsive Tpex cells
February 25, 2026
An important predictor of response to immune checkpoint blockade (ICB) is the presence of precursor exhausted T cells (Tpex) in the tumor. Conventional type 1 DCs (cDC1) are known to maintain these Tpex, and modulation of these factors might promote better therapeutic responses. In a recent publication in Nature Immunology, Lai, Chan, Armitage...
Deep and durable T cell responses after oncolytic viral therapy in glioblastoma
February 18, 2026
In a recent clinical trial, patients with glioblastoma (GBM) were treated with a single dose of an oHSV-1-based oncolytic viral therapy, rQNestin34.5v.2 (CAN-3110, linoserpaturev), in which expression of the viral ICP34.5 gene was controlled by the nestin promoter, overexpressed in GBM. Following up on evidence that treatment was associated with immune activation signatures...
Good things come in threes: results from clinical trials to improve checkpoint blockade
February 11, 2026
Immune checkpoint blockade (ICB) has become a staple in the treatment of numerous cancers, but its efficacy could still be improved. Recently, three separate clinical trials explored strategies to improve ICB in the clinic. In one study, Duttagupta, Messaoudene, et al. investigated fecal microbiome transplant (FMT) in combination with ICB in patients with...
BACH2 orchestrates T cell differentiation and can be used to optimize cellular immunotherapies
February 4, 2026
Adoptive T cell transfer (ACT) and CAR-T treatment strategies are limited in their efficacy against solid tumors, as chronic antigen exposure induces exhaustion phenotypes, with reduced proliferation and effector function, limited persistence, and reduced therapeutic efficacy as consequences. Three recent back-to-back publications in Nature Immunology assessed the role of BACH2 in these processes...
Breaking bad macrophages through remodeling with armored CAR-T
January 28, 2026
CAR T cell efficacy is limited in solid tumors due to their highly immunosuppressive tumor microenvironment (TME), which is partially and often significantly driven by tumor-associated macrophages (TAMs). Various therapies are in development to remodel the TME to improve immunotherapy efficacy. Mateus-Tique et al. developed an armored CAR-T strategy that aims to deplete...
Autocrine RA production feeds back on DC function
January 21, 2026
As professional antigen-presenting cells, dendritic cells have been utilized as whole-cell vaccines, but their clinical efficacy has thus far been limited. Fang et al. found that a common protocol of using GM-CSF and IL-4 to induce bone marrow cells (BMCs) into DCs for use in vaccines led to a decline in antigen presentation...
DC cross-presentation of dead cell F-actin antigens sculpts tumor evolution
January 14, 2026
Type 1 conventional dendritic cells (cDC1s) cross-present tumor antigens to prime CD8+ T cells. DNGR-1 on cDC1s binds to F-actin of dead cells to allow for detection and internalization of necrotic debris, and signaling results in MHC-I processing and presentation of antigens from the dead cells. In a recent publication in Nature Immunology...
Friend or foe? EPOR helps cDC1s make the call
January 7, 2026
The priming of an immune response is a complex process that is largely dependent on the functional state of cDC1s, which can induce either immunogenic or tolerogenic priming, depending on a number of conditions. While numerous factors associated with antigen uptake and presentation have been linked to different immune outcomes, the mechanisms that...
