Discovery of chemotherapy-associated ovarian cancer antigens by interrogating memory T cells

Marino Paroli (1) , Filippo Bellati (2) , Melissa Videtta (3) , Chiara Focaccetti (3) , Carmine Mancone (4) , Tiziana Donato (3) , Morena Antonilli (2) , Giorgia Perniola (2) , Daniele Accapezzato (3) , Chiara Napoletano (5) , Marianna Nuti (5) , Armando Bartolazzi (6) , Marco Tripodi (7, 8) , Fabio Palombo (3) , Vincenzo Barnaba (3, 8)

1 Dipartimento di Scienze e Biotecnologie Medico-Chirurgiche
2 UNIROMA - Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
3 Department of Internal Medicine and Medical Specialities
4 Istituto Nazionale per le Malattie Infettive I.R.C.C.S. “Lazzaro Spallanzani”
5 Department of Experimental Medicine
6 Sant'Andrea Hospital
7 Department of Cellular Biotechnologies and Haematology
8 Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti

According to the immunogenic cell death hypothesis, clinical chemotherapy treatments may result in CD8 1 and CD4 1 T-cell responses against tumor cells. To discover chemotherapy-associated antigens (CAAs), T cells derived from ovarian cancer (OC) patients (who had been treated with appropriate chemotherapy protocols) were interrogated with proteins isolated from primary OC cells. We screened for immunogenicity using two-dimensional electrophoresis gel-eluted OC proteins. Only the selected immunogenic antigens were molecularly characterized by mass-spectrometry-based analysis. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were correlated with prolonged survival in response to chemotherapy, supporting the model of chemotherapy-induced apoptosis as an adjuvant of anti-tumor immunity. The strength of both memory CD4 1 and CD8 1 T cells producing either IFN-c or IL-17 in response to apoptotic OC antigens was also significantly greater in Responders to chemotherapy than in nonresponders. Immunogenicity of some of these antigens was confirmed using recombinant proteins in an independent set of patients. The T-cell interrogation system represents a strategy of reverse tumor immunology that proposes to identify CAAs, which may then be validated as possible prognostic tumor bio-markers or cancer vaccines.

Domaines: Immunologie; Médecine humaine et pathologie; Cancer

Marino Paroli, Filippo Bellati, Melissa Videtta, Chiara Focaccetti, Carmine Mancone, et al.. Discovery of chemotherapy-associated ovarian cancer antigens by interrogating memory T cells. International Journal of Cancer. Journal International Du Cancer, 2013, pp.12. ⟨10.1002/ijc.28515⟩. ⟨pasteur-01148396⟩