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.
J Heart Lung Transplant. 2019 Apr 04;:
de Perrot M, McRae K
J Thorac Dis. 2019 Feb;11(2):602-612
Czarnecka-Kujawa K, de Perrot M, Keshavjee S, Yasufuku K
J Thorac Cardiovasc Surg. 2019 Mar 02;:
Humpl T, Honjo O, Temple M, de Perrot M
Am J Respir Crit Care Med. 2019 Apr 02;:
Goldenberg NM, Hu Y, Hu X, Volchuk A, Zhao YD, Kucherenko MM, Knosalla C, de Perrot M, Tracey KJ, Al-Abed Y, Steinberg BE, Kuebler WM
Lung Cancer. 2019 Jan;127:138-145
Wu L, Dell'Anno I, Lapidot M, Sekido Y, Chan ML, Kohno M, Serre-Beinier V, Felley-Bosco E, de Perrot M
J Thorac Dis. 2018 Nov;10(Suppl 33):S4088-S4092
de Perrot M, Cho J
Eur Respir J. 2018 Dec 13;:
Hoeper MM, Benza RL, Corris P, de Perrot M, Fadel E, Keogh AM, Kühn C, Savale L, Klepetko W
Oncologist. 2018 Nov 26;:
Soldera SV, Kavanagh J, Pintilie M, Leighl NB, de Perrot M, Cho J, Hope A, Feld R, Bradbury PA
Eur Heart J. 2018 Nov 22;:
Bibas L, Al-Kalbani M, de Perrot M, Douflé G
Support Care Cancer. 2018 Nov 14;:
Hirpara DH, Kidane B, Rogalla P, Cypel M, de Perrot M, Keshavjee S, Pierre A, Waddell T, Yasufuku K, Darling GE

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