Accelerating Cancer Immunotherapy Research (ACIR)

The tumor immune microenvironment (TIME) of ER+HER2- high-risk early breast cancer is generally immune-cold, which limits immune checkpoint blockade (ICB) responses. Since radiotherapy may modulate the immune response, it may increase ICB efficacy. However, radiotherapy may also activate the immunosuppressive CD73-adenosine pathway. Based on these hypotheses, De Caluwé et al.

Pancreatic ductal adenocarcinoma (PDA) is an aggressive and difficult-to-treat-tumor type with complex immune dynamics and multiple immune evasion mechanisms at different stages of disease. In work recently published in Science Immunology, Schmiechen et al. unraveled the roles of IFNγ-inducible MHC-I, CD8+ T cells, Tregs, and conventional CD4+ T cells (Tconv) in promoting or suppressing primary tumor growth and metastasis under conditions of immune escape and/or immunotherapy.

(1) Rodriguez C (2) Edinger RS (3) Diehl G (4) Reyes-Gonz‡lez JM (5) Lee W (6) Buckley J (7) Oh J (8) Nambiar D (9) Baidoo K (10) Okada R (11) Phadke I (12) Schmiechen Z (13) Khan H (14) Sakhalkar Y (15) Cortez AG (16) Josefsson A (17) Nedrow JR (18) White A (19) Citrin DE (20) Zhang X (21) Anderson CJ (22) Escorcia FE (23) Patel RB (24) Nguyen R Rodriguez and Edinger et al.

While accumulating evidence suggests an important role for CD4+ T cells in antitumor immunity, the specific subpopulations responsible remain to be defined. Agesta, Ferrand, et al. investigated the function of the transcription factor Eomes in CD4+ T cell antitumor responses, and identified Eomes-responsive antitumor Th populations, with significant analogies to similar Eomes-responsive CD8+ populations. Their findings were recently published in Immunity.

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.

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 to antitumor efficacy, Maltez et al.

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 tumors with elevated NMD activity.

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! Find out more here). Keynote address Elizabeth M.

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 page for our brand new spotlighted articles. Lipid nanoparticles (LNPs) have allowed for the delivery of therapeutic mRNA for various therapeutic applications.

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 al.