2024
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Personalized neoantigen vaccine improves anti-PD-1 in advanced hepatocellular carcinoma in early clinical trial
April 24, 2024
Advanced hepatocellular carcinoma (HCC) is a tumor type with a modest tumor mutation burden (TMB), low T cell infiltration, limited responses to checkpoint inhibitors, and a low patient survival rate. To overcome these hurdles, Yarchoan et al. conducted a single-arm, open-label, phase 1/2 study, in which 36 patients with advanced HCC who had...
AACR Annual Meeting 2024
April 17, 2024
Last week, the ACIR team attended the AACR Annual Meeting 2024 in San Diego, California. This week’s extensive special feature covers select talks from the conference. We have organized the content by topics below. AACR-Cancer Research Institute Lloyd J. Old AwardGordon J. Freeman Regulation of anti-tumor immunitySébastien TalbotStefani SprangerDmitry I. GabrilovichJustin Micah BalkoSjoerd...
KEYSTONE SYMPOSIA: Beyond Immune Checkpoint Blockade and Overcoming Resistance
April 10, 2024
The ACIR team attended the Keystone Symposia on Cancer Immunotherapy: Beyond Immune Checkpoint Blockade and Overcoming Resistance held on March 17-20, 2024 in Whistler, BC, 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...
Macrophage makeover required for effective CTLA-4 and ICOS combination therapy
April 3, 2024
Having previously shown that ICOS stimulation via an ICOSL-transduced B16F10 cellular vaccine (IVAX) works synergistically with CTLA-4 immune checkpoint blockade (ICB) in various murine tumor models, Sharma et al. set out to explore the mechanism of action of this synergy. In a recent publication in the Journal of Experimental Medicine, they described their...
Stem-immunity hubs predict response to anti-PD-1 in NSCLC
March 27, 2024
Chen, Nieman, and Spurrell et al. recently evaluated multicellular “immunity hubs” in samples of human non-small cell lung cancer (NSCLC) taken prior to treatment with anti-PD-1. Using imaging techniques and spatial transcriptomics, the researchers identified and characterized novel “stem-immunity hubs” that were strongly associated with PD-1 blockade responses and outcomes. Their results were...
T cells and macrophages collaborate to overcome MHC-I loss-induced immune deserts
March 20, 2024
Loss of MHC class I expression on tumor cells is a frequently observed immunotherapy resistance mechanism. The increased use of immune checkpoint blockade (ICB) for the treatment of solid tumors has resulted in more therapy-resistant MHC-I-deficient tumors. To better understand the mechanisms behind these effects and determine how to overcome this response, Beck...
CD4+ T cells help cDC1s provide CD8+ T cells with a license to kill
March 13, 2024
CD4+ T helper cells can stimulate CD8+ T cell responses by interacting with dendritic cells (DCs) through a process termed “DC licensing”. The conventional type 1 DC (cDC1) subset has been identified as the essential DC subtype for this process. Lei et al. investigated the mechanism of cDC1 licensing in human cells and...
ESMO Targeted Anticancer Therapies Congress 2024
March 6, 2024
The ACIR team attended the ESMO Targeted Anticancer Therapies Congress 2024 in Paris, France. This week’s extensive special feature covers select talks from the conference. We have organized the content by topics below. Keynote lecture on tumor neoantigensYardena Samuels BispecificsJuanita S. LopezShohei KoideGeorg Falck Antibody-drug conjugatesTakashi KagariGiuseppe CuriglianoBarbara PistilliToshio Shimizu Targeted interleukinsGiuseppe CuriglianoIgnacio...
MEGA news in gene editing: using new CRISPR technology for RNA knockdown
February 28, 2024
The CRISPR-Cas9 gene editing platform has revolutionized research and medicine by allowing for precise editing of DNA. However, these systems cannot be dynamically regulated and have limitations in their safety and efficacy. To overcome some of these limitations, Tieu et al. developed multiplexed effector guide arrays (MEGA) – a CRISPR-Cas13d platform that targets...
Taking tips from T cell cancers to improve T cell therapies
February 21, 2024
T cell therapies have been used to treat numerous cancers, but they are often limited by poor proliferation, limited persistence, immunosuppressive tumor environments, and exhaustion. In order to overcome some of these limitations, Garcia and Daniels et al. investigated naturally occurring mutations in T cell neoplasms (including clonal cells from autoinflammatory conditions and...
Antigen-specific T cells in blood predict anti-PD-1 responses in Merkel cell carcinoma
February 14, 2024
Tumor antigen-specific CD8+ T cells are known to be important in antitumor immunity, but identifying them in patient samples is often a challenge. In order to study tumor antigen-specific CD8+ T cell as potential biomarkers of response, two groups, Pulliam and Jani et al. and Ryu et al., recently evaluated them in Merkel...
Adding a personalized neoantigen vaccine to checkpoint blockade keeps resected melanoma away in a phase IIb trial
February 7, 2024
Following surgical resection of high-risk cutaneous melanoma, patients are generally treated with checkpoint inhibitors to prevent tumor recurrence, but a high proportion of patients still recur within 5 years. In an effort to reduce these recurrence rates, Weber et al. evaluated the addition of adjuvant personalized neoantigen vaccines (mRNA-4157) in a phase IIb...
CD4+ T cells wear many hats
January 31, 2024
CD4+ T cells are best known for their roles in helping CD8+ T cells, but in recent years, researchers have identified CD4+ T cells across broad ranges of subsets playing roles in activation, recruitment, reprogramming, and direct cytotoxicicity. To better understand these CD4+ T cell roles and their contributions to antitumor immunity, Bawden...
Antitumor T cell responses detected in patients with new vaccine strategy in immune-cold tumors
January 24, 2024
Colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) have a low survival rate, low infiltration of tumor-specific tumor-infiltrating lymphocytes (TIL), infrequent neoantigen mutations, and checkpoint inhibitors are largely ineffective in PDAC and subtypes of CRC. Common mutations in the oncogenes driver KRAS (mKRAS) however can serve as immunotherapy targets. Pant et al. conducted...
You can’t kill what you can't find: dormant disseminated tumor cells (DTCs) evade T cells through “relative scarcity”
January 17, 2024
Surviving breast cancer is an incredible feat, but patients whose initial tumors are successfully cleared still face a high risk of recurrence, even years after initial treatment. Tumor recurrence can be attributed to the presence of dormant disseminated tumor cells (DTCs) that hide out in the body and can potentially seed new tumors...
No more luck of the draw: new predictive signature for efficacy PD-1 blockade
January 10, 2024
Despite its successes in some patients, immune checkpoint blockade (ICB) targeting PD-1 is not beneficial in most patients with non-small cell lung cancer (NSCLC). Determining which patients would or would not benefit from this treatment has remained a challenge. Previously, a dysfunctional T cell subset has been associated with response to treatment, but...
