Immunotherapy, specifically anti-PD1, has improved patient survival in a range of tumor types including head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC). Despite the success of anti-PD1 therapy, only 20% of patients produce a durable response to this treatment. Further, there are some solid tumor types i.e. ovarian cancer, which yield very little therapeutic benefit from current standard of care immunotherapies. Thus, a need exists to develop additional therapeutic strategies to treat these patients, which includes evaluation of other tumor infiltrating immune cells that could further augment the CD8⁺ and CD4⁺ intratumoral T cell response. B cells represent a possible target for immunotherapy due to their predominance in the tumor microenvironment (TME) and crucial role in the immune response. However, B cell function in cancer and in the context of immunotherapy has been understudied. In fact, conclusions on an anti- or pro- tumor role for B cells in the TME remain incomplete. However, in multiple solid tumors, current evidence suggests an anti-tumor role for B cells.  Specifically, detection of B cells within tertiary lymphoid structures (TLS) correlates with increased survival and immunotherapeutic response.  While B cells have been identified in multiple tumor types, their complete phenotypic signature and interplay with other components within the TME have been understudied. Further, the complex composition of TLS in patient tumors is severely underappreciated, which is an overt focus of the Bruno laboratory. Specifically, we aim to understand B cell infiltration and TLS development within solid tumors to generate effective B-cell focused immunotherapies to augment the current successes of standard of care immunotherapies such as anti-PD1.

To this end, we take a multi-level approach to understanding B cells and TLS composition in human tumors. Specifically, we transcriptionally assess B cells via single cell RNAseq with paired BCR seq, we interrogate B cell subsets within patient tumors using multi-parameter flow cytometry (15-30 parameters), we locationally evaluate B cells within and outside TLS utilizing multispectral imaging (Vectra Polaris) and spatial transcriptomics (Nanostring GeoMax Digital Spatial Profiler), and we evaluate the function of B cells and their interplay with other important immune cells within the TME via micro-scale in vitro functional assays.

Biography for Tullia C. Bruno

Tullia C. Bruno, PhD, is an Assistant Professor in the Department of Immunology at the University of Pittsburgh and a faculty member in the Tumor Microenvironment Center and the Cancer Immunology and Immunotherapy Program at the UPMC Hillman Cancer Center. She obtained her Ph.D. in Immunology from Johns Hopkins in 2010 and completed her postdoctoral fellowship at the University of Colorado in 2015—both with a focus in tumor immunology.  While Dr. Bruno’s PhD training focused on inhibitory receptors on intratumoral T cells, she became interested in the role of B cells in the tumor microenvironment (TME) during her postdoctoral fellowship and has built her independent research program around understanding intratumoral B cell function within tertiary lymphoid structures in multiple human cancers.  Dr. Bruno’s research lab has an overt focus on studying immunity within cancer patients, which makes her research highly translational with the potential for future clinical trials targeting B cells. Thus, Dr. Bruno’s overall research objective is to develop a B cell-specific immunotherapy in the next five to ten years. 

Want to learn more about the importance of B cells in tertiary lymphoid structures? Check out these articles:

New predictors for immunotherapy responses sharpen our view of the tumour microenvironment

B cells and cancer - Science Direct

B cell function in the tumor microenvironment is diverse

Tertiary lymphoid structure composition is variable in cancer

More useful information about Dr. Bruno:

Complete Listing of Publications