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.
Lancet Respir Med. 2016 Nov 17;:
Yeung JC, Krueger T, Yasufuku K, de Perrot M, Pierre AF, Waddell TK, Singer LG, Keshavjee S, Cypel M
Int J Oncol. 2016 Nov 10;:
Kato T, Lee D, Wu L, Patel P, Young AJ, Wada H, Hu HP, Ujiie H, Kaji M, Kano S, Matsuge S, Domen H, Kanno H, Hatanaka Y, Hatanaka KC, Kaga K, Matsui Y, Matsuno Y, De Perrot M, Yasufuku K
J Thorac Oncol. 2016 Nov;11(11):1817-1818
Bezjak A, de Perrot M
Ann Thorac Surg. 2016 Oct 17;:
Ujiie H, Kato T, Hu HP, Hasan S, Patel P, Wada H, Lee D, Fujino K, Hwang DM, Cypel M, de Perrot M, Pierre A, Darling G, Waddell TK, Keshavjee S, Yasufuku K
J Thorac Oncol. 2016 Sep 23;
Nowak AK, Chansky K, Rice DC, Pass HI, Kindler HL, Shemanski L, Billé A, Rintoul R, Batirel HF, Thomas CF, Friedberg J, Cedres S, de Perrot M, Rusch VW, Staging and Prognostic Factors Committee, Advisory Boards and Participating Institutions
Clin Cancer Res. 2016 Sep 28;
Tsao MS, Wu L, Allo G, John T, Li M, Tagawa T, Opitz I, Anraku M, Yun Z, Pintilie M, Liu G, Pitcher B, Feld R, Johnston MR, de Perrot M
J Thorac Dis. 2016 Aug;8(8):1986-94
Donahoe LL, Nguyen ET, Chung TB, Kha LC, Cypel M, Darling GE, de Perrot M, Keshavjee S, Pierre AF, Waddell TK, Yasufuku K
Ann Thorac Surg. 2016 Sep 2;
Rusch VW, Gill R, Mitchell A, Naidich D, Rice DC, Pass HI, Kindler HL, De Perrot M, Friedberg J, Malignant Mesothelioma Volumetric CT Study Group
J Thorac Oncol. 2016 Aug;11(8):1246-62
Carbone M, Kanodia S, Chao A, Miller A, Wali A, Weissman D, Adjei A, Baumann F, Boffetta P, Buck B, de Perrot M, Dogan AU, Gavett S, Gualtieri A, Hassan R, Hesdorffer M, Hirsch FR, Larson D, Mao W, Masten S, Pass HI, Peto J, Pira E, Steele I, Tsao A,...

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