Marc de Perrot

Marc de Perrot, MD

Chemo-immunotherapy

The overall goal is to improve the outcome of mesothelioma by combining conventional chemotherapy with immunotherapy in murine mesothelioma models.

Although the first line chemotherapy composed of cisplatin and pemetrexed (Alimta) can prolong survival compared with cisplatin alone, the effect is limited. One neglected issue that has been highlighted is cancer cell repopulation during the intervals of chemotherapy. Evidence has shown that the rate of repopulation of surviving cancer cells accelerates over time. Therefore, novel approaches inhibiting this process need to be developed. Immune suppression is quite common in cancer microenvironments including mesothelioma. We attempt to improve the efficacy of chemotherapy by removing the brake of immunosuppression so as to enhance specific anti-tumour immunity. The immunosuppressive compartments such as regulatory T cells (Treg), or immunoinhibitory molecules such as CTLA-4 and PD-1 can be employed as targets to enhance T cell immune responses.

We have demonstrated that Treg cell depletion between cycles of chemotherapy has resulted in improvement of the anti-tumour effect of chemotherapy. CTLA-4 blockade expands infiltrating T cells and inhibits cancer cell repopulation between chemotherapy treatments in murine mesothelioma models.
Tech Vasc Interv Radiol. 2017 Sep;20(3):206-215
Rivers-Bowerman MD, Zener R, Jaberi A, de Perrot M, Granton J, Moriarty JM, Tan KT
Respiration. 2017 Sep 13;94(5):
Tyan CC, Machuca T, Czarnecka K, Ko HM, da Cunha Santos G, Boerner SL, Pierre A, Cypel M, Waddell T, Darling G, de Perrot M, Keshavjee S, Geddie W, Yasufuku K
BMJ Open Respir Res. 2017;4(1):e000183
Zhao YD, Yin L, Archer S, Lu C, Zhao G, Yao Y, Wu L, Hsin M, Waddell TK, Keshavjee S, Granton J, de Perrot M
In Vitro Cell Dev Biol Anim. 2017 Aug 24;:
Blum W, Pecze L, Felley-Bosco E, Worthmüller-Rodriguez J, Wu L, Vrugt B, de Perrot M, Schwaller B
Ann Thorac Surg. 2017 Aug 16;:
Donahoe L, Vanderlaan R, Thenganatt J, McRae K, Bykova A, Moric J, Granton J, de Perrot M
Clin Cancer Res. 2017 Jun 12;:
De la Maza L, Wu M, Wu L, Yun H, Zhao Y, Cattral M, McCart A, Cho J, de Perrot M
Am J Transplant. 2017 May 16;:
Avriel A, Klement AH, Johnson SR, de Perrot M, Granton J
J Thorac Cardiovasc Surg. 2017 Apr 13;:
Ujiie H, Kato T, Hu HP, Patel P, Wada H, Fujino K, Weersink R, Nguyen E, Cypel M, Pierre A, de Perrot M, Darling G, Waddell TK, Keshavjee S, Yasufuku K
Eur J Cardiothorac Surg. 2017 Apr 25;:
Moser B, Fadel E, Fabre D, Keshavjee S, de Perrot M, Thomas P, Brioude G, Van Raemdonck D, Viskens S, Lang-Lazdunski L, Bille A, Weder W, Jungraithmayr W, Ruffini E, Guerrera F, Gómez de Antonio D, Liberman M, Novoa N, Scarci M, Janik S, Klepetko W

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Director, Toronto Mesothelioma Research Program
Associate Professor, Surgery, University of Toronto