City of Hope Researchers to Present Breakthroughs in Cancer Risk, Immune Resistance, and AI-Powered Discoveries at AACR 2026

City of Hope, a leading institution in cancer research and treatment, is set to unveil groundbreaking findings at the AACR Annual Meeting 2026. This prestigious event, held from April 17–22, will showcase cutting-edge studies from City of Hope’s physicians and scientists, who will address critical challenges in understanding cancer risk, therapeutic resistance, and innovative treatment avenues across both solid and hematologic malignancies. With its National Medical Center ranked among the top cancer centers in the U.S., City of Hope continues to advance the frontier of oncology science through comprehensive, multidisciplinary research.

A highlight of this year’s presentations includes a major symposium by Dr. Stephen J. Forman, focused on the transformative potential of first-line chimeric antigen receptor (CAR) T cell therapy in adults diagnosed with acute lymphoblastic leukemia (ALL). CAR T cell therapy has revolutionized treatment paradigms for certain blood cancers by engineering a patient’s immune cells to specifically target and destroy malignant cells. Dr. Forman’s discussion will encompass clinical trial data and mechanistic insights into how initial CAR T therapy can optimize remission rates and durability for ALL patients, a population traditionally burdened with high relapse risk.

In parallel, Dr. Robert R. Jenq will deliver crucial insights into how the gut microbiome modulates patient responses to CAR T therapy. By studying the complex microbial ecosystems within patients, his research elucidates why some individuals experience remarkable therapeutic success while others encounter resistance or severe side effects. This emerging area leverages advances in metagenomics and immunology, positioning the microbiome as a key determinant of immunotherapeutic efficacy.

A standout study employs artificial intelligence (AI) to dissect gut microbiome differences implicated in early-onset colorectal cancer (CRC), a phenomenon increasingly diagnosed in younger adults. By integrating microbiome sequencing data with tumor genomics, clinical features, and social determinants of health, investigators applied sophisticated AI models to reveal reduced microbial diversity and distinct compositional shifts associated with early disease development. These findings, spearheaded by doctoral candidate Sophia Manjarrez and senior author Dr. Enrique Velazquez-Villarreal, highlight the multifactorial etiology of CRC and underscore the importance of a systems biology approach to uncover hidden biological signatures.

Another pivotal contribution from City of Hope researchers uncovers a heretofore unrecognized molecular pathway underpinning immune resistance in microsatellite-stable (MSS) colorectal cancers, which constitute the majority of CRC cases yet remain largely refractory to immunotherapy. This pathway centers on the RNA-modifying enzyme NAT10 and its interaction with the oncogene MYC. Enhanced NAT10 activity drives autophagy-mediated degradation of MHC class I molecules, essential components for T cell recognition of tumor cells. Disrupting this axis restores immune visibility of cancer cells, potentiating responses to checkpoint blockade in preclinical models. These discoveries, presented by Dr. Junyong Weng and led by Dr. Ajay Goel, offer promising therapeutic targets to overcome a major barrier in CRC treatment.

In the domain of hematologic malignancies, City of Hope’s research reveals a critical metabolic dependency in acute myeloid leukemia (AML). The protein eIF4A1 emerges as a linchpin in leukemia cell metabolism, facilitating the synthesis and utilization of nutrients necessary for unchecked proliferation. Inhibition of eIF4A1 not only impedes cellular energy production and protein translation but also translates into significant leukemia regression and survival benefits in animal models. This metabolic vulnerability, discussed by visiting researcher Xiaoxu Zhang and principal investigator Dr. Rui Su, may herald a new avenue for AML therapy by integrating metabolic repression with conventional treatments.

Advances in AI applications continue to permeate cancer immunology, exemplified by a novel model that predicts immune system targets with greater precision. This approach integrates structural predictions of peptide-MHC complexes derived from AlphaFold 3 with geometry-aware machine learning frameworks, enhancing epitope identification even when training data is limited. By refining how immune epitopes are predicted, the model may accelerate the development of personalized cancer vaccines and immunotherapies, addressing one of immunotherapy’s fundamental challenges — identifying the peptides that effectively elicit T cell responses. The work, presented by Dr. Kamel Lahouel and senior author Dr. Cristian Tomasetti, underscores the synergy between AI and experimental immunology.

City of Hope’s presence at the AACR Annual Meeting also features late-breaking poster sessions revealing novel insights into cancer disparities and immune mechanisms. For instance, spatial transcriptomics applied to endometrial cancer in African American women uncovers distinct molecular and immune pathway alterations, which may inform tailored therapeutic strategies. Additionally, studies on variations in cancer screening rates influenced by housing status and ethnicity post-implementation of targeted healthcare strategies highlight the crucial intersection of social determinants and oncologic outcomes.

The recognition of City of Hope’s scientists with multiple awards, including Early-Career Scholar and AACR Faculty Scholar honors, attests to the institution’s commitment to fostering innovative research leadership. These accolades also reflect the broader scientific community’s acknowledgment of the transformative potential of the studies being presented.

Collectively, these presentations illustrate City of Hope’s integrated approach to cancer research, encompassing molecular biology, immunology, computational modeling, and social sciences. Emphasizing translational relevance, the institution’s work aims to bridge laboratory discoveries with clinical applications, ultimately improving patient prognosis and quality of life. By embracing advanced AI, novel therapeutic targets, and comprehensive patient profiling, City of Hope is helping to define the future landscape of precision oncology.

At the heart of these endeavors lies an overarching philosophy: cancer is a multifaceted disease requiring holistic, multidisciplinary strategies. The convergence of high-throughput data technologies, innovative computational frameworks, and molecular insights is reshaping how researchers understand tumor biology, immune evasion, and therapeutic resistance. City of Hope’s presentations at AACR 2026 are a testament to the power of this model, offering hope for new, more effective treatments for patients worldwide.

As the oncology community gathers at the AACR Annual Meeting, the City of Hope team’s contributions promise to stimulate scientific dialogue and catalyze next-generation cancer therapies. From CAR T cell innovations to microbiome-mediated immune modulation and AI-driven epitope prediction, their research exemplifies the bold strides being made to unravel cancer’s complexities and translate knowledge into cures.

News Publication Date: 2026

Web References:
– https://www.cityofhope.org/
– https://www.abstractsonline.com/pp8/#!/21436/
– https://www.tgen.org/

References: Not specified in detail within the original content.