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.
Lancet Respir Med. 2019 Oct 09;:
Cypel M, Feld JJ, Galasso M, Pinto Ribeiro RV, Marks N, Kuczynski M, Kumar D, Bahinskaya I, Bagnato VS, Kurachi C, Slutsky AS, Yeung JC, Donahoe L, de Perrot M, Yasufuku K, Pierre A, Binnie M, Chaparro C, Martinu T, Chen M, Tikkanen J, Chow CW, Sidhu A...
J Thorac Cardiovasc Surg. 2019 Sep 09;:
Cypel M, Yeung JC, Donahoe L, Chen M, Zamel R, Hoetzenecker K, Yasufuku K, de Perrot M, Pierre AF, Waddell TK, Keshavjee S
JAMA Surg. 2019 Oct 09;:
Divithotawela C, Cypel M, Martinu T, Singer LG, Binnie M, Chow CW, Chaparro C, Waddell TK, de Perrot M, Pierre A, Yasufuku K, Yeung JC, Donahoe L, Keshavjee S, Tikkanen JM
Ann Thorac Surg. 2019 Oct 04;:
Tahiri M, Bykova A, Dunne B, Barth D, Donahoe L, Waddell TK, McRae K, Slinger P, Granton J, de Perrot M
J Thorac Oncol. 2019 Sep 20;:
Nicholson AG, Sauter JL, Nowak AK, Kindler HL, Gill RR, Remy-Jardin M, Armato SG, Fernandez-Cuesta L, Bueno R, Alcala N, Foll M, Pass H, Attanoos R, Baas P, Beasley MB, Brcic L, Butnor KJ, Chirieac LR, Churg A, Courtiol P, Dacic S, De Perrot M,...
Mod Pathol. 2019 Sep 04;:
Marchevsky AM, Khoor A, Walts AE, Nicholson AG, Zhang YZ, Roggli V, Carney J, Roden AC, Tazelaar HD, Larsen BT, LeStang N, Chirieac LR, Klebe S, Tsao MS, De Perrot M, Pierre A, Hwang DM, Hung YP, Mino-Kenudson M, Travis W, Sauter J, Beasley MB,...
J Thorac Oncol. 2019 Aug 27;:
Gill RR, Tsao AS, Kindler HL, Richards WG, Armato SG, Francis RJ, Gomez DR, Dahlberg S, Rimner A, Simone CB, de Perrot M, Blumenthal G, Adjei AA, Bueno R, Harpole DH, Hesdorffer M, Hirsch FR, Pass HI, Yorke E, Rosenzweig K, Burt B, Fennell DA,...
Semin Thorac Cardiovasc Surg. 2019 Aug 20;:
Yeung J, de Perrot M
Mod Pathol. 2019 Aug 02;:
Churg A, Galateau-Salle F, Roden AC, Attanoos R, von der Thusen JH, Tsao MS, Chang N, De Perrot M, Dacic S
Mol Carcinog. 2019 Jul 29;:
Lee MJ, Kuehne N, Hueniken K, Liang S, Rai S, Sorotsky H, Herman M, Shepshelovich D, Bruce J, Liang M, Patel D, Cheng D, Chen Z, Eng L, Brown MC, Cho J, Leighl NB, de Perrot M, Reisman D, Xu W, Bradbury PA, Liu G

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