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.
Int J Oncol. 2016 Aug;49(2):448-56
Kato T, Lee D, Wu L, Patel P, Young AJ, Wada H, Hu HP, Ujiie H, Kaji M, Kano S, Matsuge S, Domen H, Kaga K, Matsui Y, Kanno H, Hatanaka Y, Hatanaka KC, Matsuno Y, de Perrot M, Yasufuku K
Interact Cardiovasc Thorac Surg. 2016 Mar 30;
Donahoe L, Granton J, McRae K, Thenganatt J, Moric J, Keshavjee S, de Perrot M
Oncotarget. 2016 Mar 25;
Sacher AG, Le LW, Lara-Guerra H, Waddell TK, Sakashita S, Chen Z, Kim L, Zhang T, Kamel-Reid S, Salvarrey A, Darling G, Yasufuku K, Keshavjee S, De Perrot M, Shepherd FA, Liu G, Tsao M, Leighl NB
J Thorac Oncol. 2016 Feb 19;
Pass HI, Goparaju C, Espin-Garcia O, Donington J, Carbone M, Patel D, Chen Z, Feld R, Cho J, Gadgeel S, Wozniak A, Chachoua A, Leighl N, Tsao MS, de Perrot M, Xu W, Liu G
J Thorac Cardiovasc Surg. 2016 Jan 9;
de Perrot M, McRae K
Circulation. 2016 Jan 29;
Delcroix M, Lang I, Pepke-Zaba J, Jansa P, D'Armini AM, Snijder R, Bresser P, Torbicki A, Mellemkjaer S, Lewczuk J, Simkova I, Barberà JA, de Perrot M, Hoeper MM, Gaine S, Speich R, Gomez-Sanchez MA, Kovacs G, Jaïs X, Ambroz D, Treacy C, Morsolini M,...
J Thorac Dis. 2015 Nov;7(11):1898-906
Tagawa T, Anraku M, Morodomi Y, Takenaka T, Okamoto T, Takenoyama M, Ichinose Y, Maehara Y, Cho BC, Feld R, Tsao MS, Leighl N, Bezjak A, Keshavjee S, de Perrot M
J Thorac Cardiovasc Surg. 2015 Nov 26;
Agzarian J, Hanna WC, Schneider L, Schieman C, Finley CJ, Peysakhovich Y, Schnurr T, Nguyen-Do D, Linkins LA, Douketis J, Crowther M, De Perrot M, Waddell TK, Shargall Y

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