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

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

doi:10.3389/fonc.2019.01504

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

Front Oncol. 2020 Jan 14:9:1504. doi: 10.3389/fonc.2019.01504. eCollection 2019.

Authors

Kelly J McKelvey^{1

2

3}, Amanda L Hudson^{1

2

3}, Ramyashree Prasanna Kumar^{1

2}, Thomas Eade⁴, Stephen J Clarke^{1

2

4}, Helen R Wheeler^{1

2

3

4}, Connie I Diakos^{1

2

4}, Viive M Howell^{1

2

3}

Affiliations

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.
² Sydney Vital Translational Cancer Research Centre, Royal North Shore Hospital, St Leonards, NSW, Australia.
³ The Brain Cancer Group, St Leonards, NSW, Australia.
⁴ Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, NSW, Australia.

Abstract

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.

Keywords: cancer; immunotherapy; inflammation; radiation; toxicity.