Abstract:

It is increasingly evident that tumors respond to radiation therapy differently based on not just the inherent radiosensitivity of the tumor cells but also the ability of the immune system to eradicate them following the insult of radiation. Our interest is in exploiting critical vulnerabilities of subsets of tumors using nanoparticles and/or novel radiation strategies. First, greater T cell infiltration in solid tumors, sometimes enhanced by radiation, portends a better clinical outcomes following radiation therapy of a number of cancers. However, radiation also induces systemic lymphopenia which has a detrimental effect on treatment outcomes. I will discuss strategies to mitigate lymphopenia and improve intratumoral T cell infiltration via customized radiation treatment approaches and nanoparticle formulations. Second, the critical synapse between the tumor cell and the immune cells has been the focus of much clinical excitement in recent years. Clinical studies confirm that tumor response to radiation is dictated not only by tumor infiltration with cytotoxic T cells but also by modulation of this synapse. I will discuss strategies to either engage docking sites using nanoparticle formulations or induce the expression of docking sites to then engage with nanoparticles. Lastly, focal radiation often serves as an in-situ autovaccination strategy that is readily combined with immunostimulatory molecules to synergistically stimulate a potent systemic immune response. I will discuss nano-enabled strategies to augment this synergy optimally.

Short bio:

Dr. Krishnan is a professor in the department of radiation oncology at Mayo Clinic Florida, the director of the office of clinical trials at Mayo Florida, and a co-leader of the Mayo Clinic Cancer Center GI program. He received his medical degree from Christian Medical College, Vellore, India and completed a radiation oncology residency at the Mayo Clinic, Rochester, Minnesota. He then worked at MD Anderson Cancer Center in Houston for 15 years where he was the Director of the Center for Radiation Oncology Research and the John E. and Dorothy J. Harris professor of gastrointestinal cancer. In the clinic, he treats patients with hepatobiliary, pancreatic and rectal tumors with radiation therapy. His laboratory has developed new strategies for sensitizing tumors to radiation therapy using botanicals, targeted therapies, chemotherapy and nanoparticles. He serves as the chair of the gastrointestinal scientific program committee of ASTRO, chair of the gastrointestinal education committee of ASTRO, co-chair of the gastrointestinal translational research program of NRG, consultant to the IAEA for rectal and liver cancers, chair of the NCI pancreatic cancer radiotherapy working group, and Fellow of the American College of Physicians and ASTRO. He has co-authored over 250 peer-reviewed scientific publications with an h-index > 75, co-authored 18 book chapters, co-edited 3 books, co-patented 6 inventions, and served on the editorial board of over a dozen journals.

There is no recording of this session due to inclusion of unpublished data.