RT Journal Article
SR Electronic
T1 The Goldilocks Window of Personalized Chemotherapy: An Immune Perspective
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 495184
DO 10.1101/495184
A1 Derek S. Park
A1 Mark Robertson-Tessi
A1 Philip K. Maini
A1 Michael B. Bonsall
A1 Robert A. Gatenby
A1 Alexander R. A. Anderson
YR 2018
UL http://biorxiv.org/content/early/2018/12/13/495184.abstract
AB The immune system is increasingly being recognized for its untapped potential in being recruited to attack tumors in cancer therapy. The main challenge, however, is that most tumors exist in a state of immune tolerance where the patient’s immune system has become insensitive to the cancer cells. In order to investigate the ability to use chemotherapy to break immune tolerance, we created a mathematical modeling framework for tumor-immune dynamics. Our results suggest that optimal chemotherapy scheduling must balance two opposing objectives: maximal tumor reduction and preserving patient immune function. Successful treatment requires therapy to operate in a ‘Goldilocks Window’ where patient immune health is not overly compromised. By keeping therapy ‘just right’, we show that the synergistic effects of immune activation and chemotherapy can maximize tumor reduction and control.Statement of Significance In order to maximize the synergy between chemotherapy and anti-tumor immune response, lymphodepleting therapy must be balanced in a ‘Goldilocks Window’ of optimal dosing.