A Coordinated Campaign to Cure Cancer

Immune cell mechanisms

This is where it starts. Our work here maps the basic mechanisms of T cell activation, exhaustion and memory formation in the tumor context, and the innate–adaptive immune crosstalk that shapes how the body fights back. Understanding exactly how immune cells traffic into and through tumors is foundational; it's what the rest of the institute's work builds on. Work here includes T cells, B cells, dendritic cells, NK cells, macrophages and more.

Activating T cells

This is the discovery that changed cancer treatment, and it's not finished yet. Priorities include identifying and validating next-generation checkpoint targets beyond PD-1/PD-L1 and CTLA-4 and building combination strategies that pair checkpoint blockade with other modalities. Understanding the mechanisms of resistance, paired with biomarkers that guide patient selection, is how the next wave of cures gets built.

Effective treatments to clinic

This is where discovery becomes medicine. Translational trial design pairs mechanistic hypotheses with real clinical outcomes, while longitudinal immune monitoring platforms track response and resistance in real time, so no signal goes unnoticed. It's also where the institute's Immunotherapy Platform support initiative lives operationally: expanding sequencing, spatial omics and data science capacity so rigorous science reaches further across UT MD Anderson, turning more patients' samples into insight.

Immune-microbe interactions

The microbiome is an unexpected ally in the fight against cancer. Research here shows how gut and tumor-associated microbiota shape response to immunotherapy, and it's turning up microbiome-based biomarkers of response and toxicity along the way. From there, the path leads to live biotherapeutics and microbiota-modulating adjuvants that could help checkpoint blockade work for more patients, backed by work linking microbial ecology to immune cell function.

Priming immune response

Training the immune system to recognize and eliminate cells bearing mutations has been enabled by the power of immune checkpoint blockade and genomics. Personalized neoantigen vaccines and off-the-shelf, shared-antigen platforms are both in active development, alongside adjuvant and delivery innovations built to work in combination with checkpoint blockade. The field is also expanding into new territory: a growing number of trials are now testing cancer vaccines to eliminate premalignant lesions before they ever become cancer, not just treat disease that has already developed, though that specific application sits outside the Institute's current vaccine program. This is one of the institute's four core strategic initiatives, currently anchored by Betty Kim's lab and its glioblastoma-focused delivery platform, with a dedicated recruit still to come.

Cancer-genome interactions

Cracking the code of why some tumors respond to immunotherapy and others don't: In metastatic bladder cancer specifically, this domain identified ARID1A mutation paired with CXCL13 expression, not ARID1A alone, as a combination biomarker that predicts response to checkpoint therapy. On the resistance side, elevated EZH2 expression in regulatory T cells was identified as a T cell–intrinsic driver of resistance to anti-CTLA-4 therapy, a finding that has already led to an active clinical trial combining an EZH1/2 inhibitor with ipilimumab in genitourinary cancers. Alongside this work, the domain more broadly pioneers epigenetic reprogramming strategies that make tumors more visible to the immune system. It's the institute's formal biomarker/resistance initiative, anchored specifically in the Goswami Lab's pursuit of ARID1A and EZH2, and it's already reshaping how patients get matched to treatment.

Manipulating new targets

Where chemistry meets ambition: Both new chemical tools and AI-guided protein design are being used to reach targets long dismissed as undruggable, giving researchers new ways to interrogate and manipulate immune signaling pathways. This work extends into engineered biologics, including molecular glue degraders and synthetic proteins. This is the fourth core strategic initiative, envisioned around four investigators, with three more positions still to be filled.

Cell-cell relationships

Turning oceans of data into a map of the tumor-immune battlefield: Spatial multi-omics and AI/ML models give researchers a cell-by-cell view of how tumors and the immune system interact, generating fresh hypotheses that ripple out to every other domain in the Institute. It's also the engine behind the Immunotherapy Platform support initiative, extending sequencing and spatial omics capacity across UT MD Anderson so the institute's reach keeps growing.