Sub-acute Toxicity in Non-cancerous Tissue and Immune-Related Adverse Events of a Novel Combination Therapy for Cancer

oleh: Kelly J. McKelvey, Kelly J. McKelvey, Kelly J. McKelvey, Amanda L. Hudson, Amanda L. Hudson, Amanda L. Hudson, Ramyashree Prasanna Kumar, Ramyashree Prasanna Kumar, Thomas Eade, Stephen J. Clarke, Stephen J. Clarke, Stephen J. Clarke, Helen R. Wheeler, Helen R. Wheeler, Helen R. Wheeler, Helen R. Wheeler, Connie I. Diakos, Connie I. Diakos, Connie I. Diakos, Viive M. Howell, Viive M. Howell, Viive M. Howell

Format: Article
Diterbitkan: Frontiers Media S.A. 2020-01-01

Deskripsi

Brain, lung, and colon tissue experience deleterious immune-related adverse events when immune-oncological agents or radiation are administered. However, there is a paucity of information regarding whether the addition of radiation to immuno-oncological regimens exacerbates the tissue inflammatory response. We used a murine model to evaluate sub-acute tissue damage and the systemic immune response in C57Bl/6 mice when administered systemic anti-programmed cell death protein 1 (αPD-1) immunotherapy alone or in combination with stereotactic fractionated 10 gray/5 X-ray radiation to normal brain, lung or colon tissue. The model indicated that combinatorial αPD-1 immunotherapy and radiation may alter normal colon cell proliferation and cerebral blood vasculature, and induce systemic thrombocytopenia, lymphopenia, immune suppression, and altered immune repertoire (including interleukin-1β). Therein our data supports close monitoring of hematological and immune-related adverse events in patients receiving combination therapy.