Zachary Morris

In the Morris Lab, we are focused on using preclinical and translational research approaches to study the mechanisms whereby radiation may impact the anti-tumor response to immunotherapies. Our primary objective is to determine whether and how radiation may optimally be employed to simultaneously modulate the tumor immune microenvironment and to increase the susceptibility of tumor cells to immune response. We seek to test these approaches in early phase clinical studies where they may be further refined with the ultimate aim of improving survival and achieving cures in patients with metastatic cancers.

In situ tumor vaccination is a therapeutic strategy that seeks to convert a patient’s own tumor into a nidus for enhanced presentation of tumor-specific antigens in a way that will stimulate and diversify an anti-tumor T cell response. Radiation therapy elicits an anti-tumor effect through induction of DNA damage in tumor cells, yet it has long been recognized that host immune capability and tumor immune susceptibility modulate the sensitivity of a tumor to radiation. The mechanisms by which local radiation may interact with the immune system include release of tumor-specific antigens, phenotypic changes in tumor cell expression of immune susceptibility markers and local eradication of suppressive immune cell lineages. By modulating tumor immune tolerance and functional immunogenicity at a targeted site, radiation may serve as a method of in situ tumor vaccination. Multiple preclinical studies demonstrate that random tumor-specific protein mutations are among the most immunogenic tumor antigens recognized by T cells. By rendering such antigens accessible to immune recognition, radiation may augment the local and systemic anti-tumor response to immunotherapy. If proven effective, such combinations might transform RT from a predominantly loco-regional treatment to a critical component of systemic therapy.

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