MD Anderson Experts Spotlight Key Immunotherapy Advances at 2025 SITC Annual Meeting

As immunotherapy continues to transform cancer care, researchers at The University of Texas MD Anderson Cancer Center shared new insights at the 2025 Society for Immunotherapy of Cancer (SITC) Annual Meeting about how the immune system can be trained, guided and strengthened to improve patient outcomes.

MD Anderson scientists and clinicians presented nearly 30 abstracts and lectures at this year’s meeting. Below is a selection of key questions that were addressed in oral abstracts and presentations.

Could the gut microbiome be key to improving immunotherapy responses?

Jennifer Wargo, M.D., professor of Surgical Oncology and Genomic Medicine, Deputy Director of MD Anderson’s National Cancer Institute (NCI)-designated Cancer Center Support Grant, and core member of the James P. Allison Institute, leads the field in uncovering how the gut microbiome influences the immune system and immunotherapy outcomes. Her team has demonstrated that patients with diverse gut microbiomes and an increased abundance of specific microbial taxa respond better to immune checkpoint inhibitors. The team also showed that factors like diet and antibiotic use can shape those responses. Wargo and her colleagues are exploring novel approaches, such as diet interventions and synthetic microbiome therapies, to improve treatment outcomes in patients with melanoma and other cancers. Wargo presented the keynote address Nov. 7.

Can immunotherapy be used for cancer prevention?

Precancer interception remains an aspirational goal in immuno-oncology. In a Nov. 7 presentation, Jianjun Zhang, M.D., Ph.D., assistant professor of Thoracic/Head and Neck Oncology and Genomic Medicine, will discuss how manipulating the immune landscape in precancerous lung tissue may delay or even prevent tumor formation. Lung cancer is often detected at a late stage, when treatment and outcomes are poor. Zhang’s research aims to catch the disease early in a pre-tumor stage and map how the immune system changes in order to intervene early. This is promising for designing immunoprevention therapies.

Can we improve outcomes for patients with EGFR-positive lung cancer whose disease has progressed after targeted therapy?

Xiuning Le, M.D., Ph.D., associate professor of Thoracic/Head and Neck Oncology, presented final overall survival results from the Phase III HARMONi-A trial. These data demonstrate improved survival with ivonescimab – a novel PD-1/VEGF bispecific antibody – combined with chemotherapy versus chemotherapy alone in patients with EGFR-mutated non-small cell lung cancer (NSCLC) whose disease has progressed after targeted therapy. These findings highlight ivonescimab’s potential to fill a critical gap for patients who have limited options after targeted therapy failure, positioning it as a promising new approach that addresses both tumor immune evasion and angiogenesis. Le presented the trial results Nov. 7 (Abstract 1348).

What can B cells teach us about lasting treatment responses?

Alessandra Vaccaro, Ph.D., postdoctoral fellow in Thoracic/Head and Neck Oncology, led a study exploring how B-cell driven immunity shapes outcomes in immunotherapy treated NSCLC. Research suggests that patients whose tumors contain clusters of B and T cells, known as tertiary lymphoid structures, may have stronger responses to treatment. This new model may provide more precise immunotherapy strategies and offer potential pathways to boost durable responses in some lung cancer patients. Vaccaro presented the findings Nov. 7 (Abstract 709).

How does the nervous system affect immune activity?

Moran Amit, M.D., Ph.D., assistant professor of Head and Neck Surgery and Genomic Medicine, emphasizes that the nervous system is a critical component of the tumor microenvironment. His research highlights how neural activity can shape immune cell behavior, influence tumor growth and affect patients’ responses to immunotherapy. By understanding how nerve-immune interactions drive tumor progression, his research aims to uncover new therapeutic strategies for head and neck cancer patients and other solid tumors. Amit presented on Nov. 7.

Can imaging predict which patients will respond to immunotherapy?

Stephane Champiat, M.D., Ph.D., associate professor of Investigational Cancer Therapeutics, shared how radiomics and artificial intelligence (AI)-based image analysis can uncover hidden biomarkers that non-invasively predict patient response to immunotherapy, identify potential toxicities, and help design more efficient clinical trials. The integration of radiomics with genomics and other data types is seen as a future step toward more precise cancer treatment strategies. Champiat presented on Nov. 8.

How might mRNA vaccines make “cold” tumors responsive to treatment?

Adam Grippin, M.D., Ph.D., senior resident in Radiation Oncology, discovered that mRNA vaccine technology can activate immune cells against tumors that previously resisted immunotherapy. This study showed mRNA vaccines, even those not specifically targeting cancer, can transform immunologically "cold" tumors by triggering an immune response that allows T cells to infiltrate and target tumor cells. This mechanism involves activating antigen-presenting cells and inducing cancer cells to express PD-L1, making them vulnerable when combined with immune checkpoint inhibitors. These findings were presented at the 2025 European Society for Medical Oncology (ESMO) Congress and published in Nature. Grippin presented updated results Nov. 8 (Abstract 419).

What’s new in understanding why some tumors escape immune attack?

Dustin McCurry, M.D., instructor of Lymphoma/Myeloma, led researchers in identifying a previously unknown pathway by which leukemia cells hide from the immune system. They found that oncogenic mutations in ASXL 1 changed how cancer cells display critical immune markers that enable immune attack. This change allowed the cancer cells to evade detection and resist treatment. Using CRISPR gene editing, the team showed that correcting this mutation made the cancer cells visible again to immune attack. These data unearth a new mechanism by which oncogenic mutations can avoid immune destruction. McCurry presented the findings Nov. 8 (Abstract 1228).

How can radiation therapy activate the immune system?

Research led by Robert Saddawi-Konefka, M.D., Ph.D., fellow in Head and Neck Surgery, examined how tumor-directed radiation can reprogram migratory dendric cells that drive tumor rejection. These CCR7* dendritic cells migrate from tumors to sentinel lymph nodes and are key to activating anti-tumor immunity. Sequencing therapies with tumor-directed, lymphatic-sparing radiotherapy, followed by anti PD-1 immunotherapy, produced the strongest tumor response, leading to durable tumor control and immunologic memory. This study demonstrates that lymphatic-sparing radiotherapy enhances immunotherapy by promoting dendritic cell tumor surveillance and migration, converting immune tolerance into effective antitumor immunity. Saddawi-Konefka presented the findings in the Presidential Session Nov. 9 (Abstract 676).