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

Frontiers in Oncology

Thomas Eade²  Stephen J. Clarke²  Helen R. Wheeler²  Connie I. Diakos²  Ramyashree Prasanna Kumar³  Viive M. Howell⁴  Kelly J. McKelvey⁴  Amanda L. Hudson⁴ 

[1] Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, The University of Sydney Northern Clinical School and Northern Sydney Local Health District, St Leonards, NSW, Australia;Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, NSW, Australia;Sydney Vital Translational Cancer Research Centre, Royal North Shore Hospital, St Leonards, NSW, Australia;The Brain Cancer Group, St Leonards, NSW, Australia;

关键词: cancer;    radiation;    immunotherapy;    inflammation;    toxicity;   

DOI  :  10.3389/fonc.2019.01504

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown