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27 results on '"Cattaneo, Chiara M."'

1. Base editing screens define the genetic landscape of cancer drug resistance mechanisms

Author

Coelho, Matthew A., Strauss, Magdalena E., Watterson, Alex, Cooper, Sarah, Bhosle, Shriram, Illuzzi, Giuditta, Karakoc, Emre, Dinçer, Cansu, Vieira, Sara F., Sharma, Mamta, Moullet, Marie, Conticelli, Daniela, Koeppel, Jonas, McCarten, Katrina, Cattaneo, Chiara M., Veninga, Vivien, Picco, Gabriele, Parts, Leopold, Forment, Josep V., Voest, Emile E., Marioni, John C., Bassett, Andrew, and Garnett, Mathew J.

Published
2024
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3. Taxanes trigger cancer cell killing in vivo by inducing non-canonical T cell cytotoxicity

Author

Vennin, Claire, Cattaneo, Chiara M., Bosch, Leontien, Vegna, Serena, Ma, Xuhui, Damstra, Hugo G.J., Martinovic, Moreno, Tsouri, Efi, Ilic, Mila, Azarang, Leyla, van Weering, Jan R.T., Pulver, Emilia, Zeeman, Amber L., Schelfhorst, Tim, Lohuis, Jeroen O., Rios, Anne C., Dekkers, Johanna F., Akkari, Leila, Menezes, Renee, Medema, Rene, Baglio, Serena R., Akhmanova, Anna, Linn, Sabine C., Lemeer, Simone, Pegtel, Dirk M., Voest, Emile E., and van Rheenen, Jacco

Published
2023
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5. Data from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy

Author

Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary

Published
2023
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6. Supplementary Figure 4 from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy

Author

Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary

Published
2023
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7. Supplementary Figure 5 from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy

Author

Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary

Published
2023
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8. Supplementary Figure 1 from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy

Author

Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary

Published
2023
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9. Supplementary Table 1 from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy

Author

Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary

Published
2023
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10. Supplementary Figure 3 from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy

Author

Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary

Published
2023
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11. Supplementary Figure 2 from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy

Author

Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary

Published
2023
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12. Cell Model Network-UK from Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy

Author

Picco, Gabriele, primary, Cattaneo, Chiara M., primary, van Vliet, Esmée J., primary, Crisafulli, Giovanni, primary, Rospo, Giuseppe, primary, Consonni, Sarah, primary, Vieira, Sara F., primary, Rodríguez, Iñigo Sánchez, primary, Cancelliere, Carlotta, primary, Banerjee, Ruby, primary, Schipper, Luuk J., primary, Oddo, Daniele, primary, Dijkstra, Krijn K., primary, Cinatl, Jindrich, primary, Michaelis, Martin, primary, Yang, Fengtang, primary, Di Nicolantonio, Federica, primary, Sartore-Bianchi, Andrea, primary, Siena, Salvatore, primary, Arena, Sabrina, primary, Voest, Emile E., primary, Bardelli, Alberto, primary, and Garnett, Mathew J., primary

Published
2023
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13. Taxanes trigger cancer cell killing in vivo by inducing non-canonical T cell cytotoxicity

Author

Sub Cell Biology, Sub Biomol.Mass Spectrometry & Proteom., Cell Biology, Neurobiology and Biophysics, Biomolecular Mass Spectrometry and Proteomics, Vennin, Claire, Cattaneo, Chiara M, Bosch, Leontien, Vegna, Serena, Ma, Xuhui, Damstra, Hugo G J, Martinovic, Moreno, Tsouri, Efi, Ilic, Mila, Azarang, Leyla, van Weering, Jan R T, Pulver, Emilia, Zeeman, Amber L, Schelfhorst, Tim, Lohuis, Jeroen O, Rios, Anne C, Dekkers, Johanna F, Akkari, Leila, Menezes, Renee, Medema, Rene, Baglio, Serena R, Akhmanova, Anna, Linn, Sabine C, Lemeer, Simone, Pegtel, Dirk M, Voest, Emile E, van Rheenen, Jacco, Sub Cell Biology, Sub Biomol.Mass Spectrometry & Proteom., Cell Biology, Neurobiology and Biophysics, Biomolecular Mass Spectrometry and Proteomics, Vennin, Claire, Cattaneo, Chiara M, Bosch, Leontien, Vegna, Serena, Ma, Xuhui, Damstra, Hugo G J, Martinovic, Moreno, Tsouri, Efi, Ilic, Mila, Azarang, Leyla, van Weering, Jan R T, Pulver, Emilia, Zeeman, Amber L, Schelfhorst, Tim, Lohuis, Jeroen O, Rios, Anne C, Dekkers, Johanna F, Akkari, Leila, Menezes, Renee, Medema, Rene, Baglio, Serena R, Akhmanova, Anna, Linn, Sabine C, Lemeer, Simone, Pegtel, Dirk M, Voest, Emile E, and van Rheenen, Jacco

Published
2023

14. Taxanes trigger cancer cell killing in vivo by inducing non-canonical T cell cytotoxicity

Author

CMM Sectie Molecular Cancer Research, Cancer, Pathologie, Externen Med. Onco, Hubrecht Institute with UMC, Vennin, Claire, Cattaneo, Chiara M., Bosch, Leontien, Vegna, Serena, Ma, Xuhui, Damstra, Hugo G.J., Martinovic, Moreno, Tsouri, Efi, Ilic, Mila, Azarang, Leyla, van Weering, Jan R.T., Pulver, Emilia, Zeeman, Amber L., Schelfhorst, Tim, Lohuis, Jeroen O., Rios, Anne C., Dekkers, Johanna F., Akkari, Leila, Menezes, Renee, Medema, Rene, Baglio, Serena R., Akhmanova, Anna, Linn, Sabine C., Lemeer, Simone, Pegtel, Dirk M., Voest, Emile E., van Rheenen, Jacco, CMM Sectie Molecular Cancer Research, Cancer, Pathologie, Externen Med. Onco, Hubrecht Institute with UMC, Vennin, Claire, Cattaneo, Chiara M., Bosch, Leontien, Vegna, Serena, Ma, Xuhui, Damstra, Hugo G.J., Martinovic, Moreno, Tsouri, Efi, Ilic, Mila, Azarang, Leyla, van Weering, Jan R.T., Pulver, Emilia, Zeeman, Amber L., Schelfhorst, Tim, Lohuis, Jeroen O., Rios, Anne C., Dekkers, Johanna F., Akkari, Leila, Menezes, Renee, Medema, Rene, Baglio, Serena R., Akhmanova, Anna, Linn, Sabine C., Lemeer, Simone, Pegtel, Dirk M., Voest, Emile E., and van Rheenen, Jacco

Published
2023

15. Genetic and pharmacological modulation of DNA mismatch repair heterogeneous tumors promotes immune surveillance

Author

Amodio, Vito, primary, Lamba, Simona, additional, Chilà, Rosaria, additional, Cattaneo, Chiara M., additional, Mussolin, Benedetta, additional, Corti, Giorgio, additional, Rospo, Giuseppe, additional, Berrino, Enrico, additional, Tripodo, Claudio, additional, Pisati, Federica, additional, Bartolini, Alice, additional, Aquilano, Maria Costanza, additional, Marsoni, Silvia, additional, Mauri, Gianluca, additional, Marchiò, Caterina, additional, Abrignani, Sergio, additional, Di Nicolantonio, Federica, additional, Germano, Giovanni, additional, and Bardelli, Alberto, additional

Published
2023
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16. Base editing screens map mutations affecting interferon-γ signaling in cancer

Author

Coelho, Matthew A., primary, Cooper, Sarah, additional, Strauss, Magdalena E., additional, Karakoc, Emre, additional, Bhosle, Shriram, additional, Gonçalves, Emanuel, additional, Picco, Gabriele, additional, Burgold, Thomas, additional, Cattaneo, Chiara M., additional, Veninga, Vivien, additional, Consonni, Sarah, additional, Dinçer, Cansu, additional, Vieira, Sara F., additional, Gibson, Freddy, additional, Barthorpe, Syd, additional, Hardy, Claire, additional, Rein, Joel, additional, Thomas, Mark, additional, Marioni, John, additional, Voest, Emile E., additional, Bassett, Andrew, additional, and Garnett, Mathew J., additional

Published
2023
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18. Identification of patient-specific CD4+ and CD8+ T cell neoantigens through HLA-unbiased genetic screens.

Author

Cattaneo, Chiara M., Battaglia, Thomas, Urbanus, Jos, Moravec, Ziva, Voogd, Rhianne, de Groot, Rosa, Hartemink, Koen J., Haanen, John B. A. G., Voest, Emile E., Schumacher, Ton N., and Scheper, Wouter

Abstract

Cancer neoantigens that arise from tumor mutations are drivers of tumor-specific T cell responses, but identification of T cell-recognized neoantigens in individual patients is challenging. Previous methods have restricted antigen discovery to selected HLA alleles, thereby limiting the breadth of neoantigen repertoires that can be uncovered. Here, we develop a genetic neoantigen screening system that allows sensitive identification of CD4+ and CD8+ T cell-recognized neoantigens across patients' complete HLA genotypes. Patient-specific tumor neoantigens are recognized by T cells. [ABSTRACT FROM AUTHOR]

Published
2023
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19. Base editing screens map mutations affecting IFNγ signalling in cancer

Author

Coelho, Matthew A., primary, Karakoc, Emre, additional, Bhosle, Shriram, additional, Gonçalves, Emanuel, additional, Burgold, Thomas, additional, Cooper, Sarah, additional, Cattaneo, Chiara M., additional, Veninga, Vivien, additional, Consonni, Sarah, additional, Dinçer, Cansu, additional, Vieira, Sara F., additional, Gibson, Freddy, additional, Barthorpe, Syd, additional, Hardy, Claire, additional, Rein, Joel, additional, Thomas, Mark, additional, Voest, Emile, additional, Bassett, Andrew, additional, and Garnett, Mathew J., additional

Published
2022
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20. Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair–Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy

Author

Picco, Gabriele, primary, Cattaneo, Chiara M., additional, van Vliet, Esmée J., additional, Crisafulli, Giovanni, additional, Rospo, Giuseppe, additional, Consonni, Sarah, additional, Vieira, Sara F., additional, Rodríguez, Iñigo Sánchez, additional, Cancelliere, Carlotta, additional, Banerjee, Ruby, additional, Schipper, Luuk J., additional, Oddo, Daniele, additional, Dijkstra, Krijn K., additional, Cinatl, Jindrich, additional, Michaelis, Martin, additional, Yang, Fengtang, additional, Di Nicolantonio, Federica, additional, Sartore-Bianchi, Andrea, additional, Siena, Salvatore, additional, Arena, Sabrina, additional, Voest, Emile E., additional, Bardelli, Alberto, additional, and Garnett, Mathew J., additional

Published
2021
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21. Tumor organoid–T-cell coculture systems

Author

Hubrecht Institute with UMC, Cattaneo, Chiara M., Dijkstra, Krijn K., Fanchi, Lorenzo F., Kelderman, Sander, Kaing, Sovann, van Rooij, Nienke, van den Brink, Stieneke, Schumacher, Ton N., Voest, Emile E., Hubrecht Institute with UMC, Cattaneo, Chiara M., Dijkstra, Krijn K., Fanchi, Lorenzo F., Kelderman, Sander, Kaing, Sovann, van Rooij, Nienke, van den Brink, Stieneke, Schumacher, Ton N., and Voest, Emile E.

Published
2020

22. Tumor organoid–T-cell coculture systems

Author

Cattaneo, Chiara M., primary, Dijkstra, Krijn K., additional, Fanchi, Lorenzo F., additional, Kelderman, Sander, additional, Kaing, Sovann, additional, van Rooij, Nienke, additional, van den Brink, Stieneke, additional, Schumacher, Ton N., additional, and Voest, Emile E., additional

Published
2019
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23. Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Author

Dijkstra, Krijn K., Cattaneo, Chiara M., Weeber, Fleur, Chalabi, Myriam, van de Haar, Joris, Fanchi, Lorenzo F., Slagter, Maarten, van der Velden, Daphne L., Kaing, Sovann, Kelderman, Sander, van Rooij, Nienke, van Leerdam, Monique E., Depla, Annekatrien, Smit, Egbert F., Hartemink, Koen J., de Groot, Rosa, Wolkers, Monika C., Sachs, Norman, Snaebjornsson, Petur, Monkhorst, Kim, Haanen, John, Clevers, Hans, Schumacher, Ton N., Voest, Emile E., Dijkstra, Krijn K., Cattaneo, Chiara M., Weeber, Fleur, Chalabi, Myriam, van de Haar, Joris, Fanchi, Lorenzo F., Slagter, Maarten, van der Velden, Daphne L., Kaing, Sovann, Kelderman, Sander, van Rooij, Nienke, van Leerdam, Monique E., Depla, Annekatrien, Smit, Egbert F., Hartemink, Koen J., de Groot, Rosa, Wolkers, Monika C., Sachs, Norman, Snaebjornsson, Petur, Monkhorst, Kim, Haanen, John, Clevers, Hans, Schumacher, Ton N., and Voest, Emile E.

Published
2018

24. Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Author

Dijkstra, Krijn K, Cattaneo, Chiara M, Weeber, Fleur, Chalabi, Myriam, van de Haar, Joris, Fanchi, Lorenzo F, Slagter, Maarten, van der Velden, Daphne L, Kaing, Sovann, Kelderman, Sander, van Rooij, Nienke, van Leerdam, Monique E, Depla, Annekatrien, Smit, Egbert F, Hartemink, Koen J, de Groot, Rosa, Wolkers, Monika C, Sachs, Norman, Snaebjornsson, Petur, Monkhorst, Kim, Haanen, John, Clevers, Hans, Schumacher, Ton N, Voest, Emile E, Dijkstra, Krijn K, Cattaneo, Chiara M, Weeber, Fleur, Chalabi, Myriam, van de Haar, Joris, Fanchi, Lorenzo F, Slagter, Maarten, van der Velden, Daphne L, Kaing, Sovann, Kelderman, Sander, van Rooij, Nienke, van Leerdam, Monique E, Depla, Annekatrien, Smit, Egbert F, Hartemink, Koen J, de Groot, Rosa, Wolkers, Monika C, Sachs, Norman, Snaebjornsson, Petur, Monkhorst, Kim, Haanen, John, Clevers, Hans, Schumacher, Ton N, and Voest, Emile E

Abstract

Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer. Furthermore, we demonstrate that these T cells can be used to assess the efficiency of killing of matched tumor organoids. This platform provides an unbiased strategy for the isolation of tumor-reactive T cells and provides a means by which to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient.

Published
2018

25. Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Author

Cancer, Child Health, Regenerative Medicine and Stem Cells, Hubrecht Institute with UMC, Dijkstra, Krijn K., Cattaneo, Chiara M., Weeber, Fleur, Chalabi, Myriam, van de Haar, Joris, Fanchi, Lorenzo F., Slagter, Maarten, van der Velden, Daphne L., Kaing, Sovann, Kelderman, Sander, van Rooij, Nienke, van Leerdam, Monique E., Depla, Annekatrien, Smit, Egbert F., Hartemink, Koen J., de Groot, Rosa, Wolkers, Monika C., Sachs, Norman, Snaebjornsson, Petur, Monkhorst, Kim, Haanen, John, Clevers, Hans, Schumacher, Ton N., Voest, Emile E., Cancer, Child Health, Regenerative Medicine and Stem Cells, Hubrecht Institute with UMC, Dijkstra, Krijn K., Cattaneo, Chiara M., Weeber, Fleur, Chalabi, Myriam, van de Haar, Joris, Fanchi, Lorenzo F., Slagter, Maarten, van der Velden, Daphne L., Kaing, Sovann, Kelderman, Sander, van Rooij, Nienke, van Leerdam, Monique E., Depla, Annekatrien, Smit, Egbert F., Hartemink, Koen J., de Groot, Rosa, Wolkers, Monika C., Sachs, Norman, Snaebjornsson, Petur, Monkhorst, Kim, Haanen, John, Clevers, Hans, Schumacher, Ton N., and Voest, Emile E.

Published
2018

26. Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Author

Dijkstra, Krijn K., primary, Cattaneo, Chiara M., additional, Weeber, Fleur, additional, Chalabi, Myriam, additional, van de Haar, Joris, additional, Fanchi, Lorenzo F., additional, Slagter, Maarten, additional, van der Velden, Daphne L., additional, Kaing, Sovann, additional, Kelderman, Sander, additional, van Rooij, Nienke, additional, van Leerdam, Monique E., additional, Depla, Annekatrien, additional, Smit, Egbert F., additional, Hartemink, Koen J., additional, de Groot, Rosa, additional, Wolkers, Monika C., additional, Sachs, Norman, additional, Snaebjornsson, Petur, additional, Monkhorst, Kim, additional, Haanen, John, additional, Clevers, Hans, additional, Schumacher, Ton N., additional, and Voest, Emile E., additional

Published
2018
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27. Genetic and pharmacological modulation of DNA mismatch repair heterogeneous tumors promotes immune surveillance

Author

Vito Amodio, Simona Lamba, Rosaria Chilà, Chiara M. Cattaneo, Benedetta Mussolin, Giorgio Corti, Giuseppe Rospo, Enrico Berrino, Claudio Tripodo, Federica Pisati, Alice Bartolini, Maria Costanza Aquilano, Silvia Marsoni, Gianluca Mauri, Caterina Marchiò, Sergio Abrignani, Federica Di Nicolantonio, Giovanni Germano, Alberto Bardelli, Amodio, Vito, Lamba, Simona, Chilà, Rosaria, Cattaneo, Chiara M, Mussolin, Benedetta, Corti, Giorgio, Rospo, Giuseppe, Berrino, Enrico, Tripodo, Claudio, Pisati, Federica, Bartolini, Alice, Aquilano, Maria Costanza, Marsoni, Silvia, Mauri, Gianluca, Marchiò, Caterina, Abrignani, Sergio, Di Nicolantonio, Federica, Germano, Giovanni, and Bardelli, Alberto

Subjects
Cancer Research, 6-thioguanine, mismatch repair, Oncology, heterogeneity, immune checkpoint blockade, immune evasion, immune surveillance, microsatellite unstable tumors (MSI), temozolomide, 6-thioguanine, heterogeneity, immune checkpoint blockade, immune evasion, immune surveillance, microsatellite unstable tumors (MSI), mismatch repair, temozolomide, Settore MED/08 - Anatomia Patologica
Abstract

Patients affected by colorectal cancer (CRC) with DNA mismatch repair deficiency (MMRd), often respond to immune checkpoint blockade therapies, while those with mismatch repair-proficient (MMRp) tumors generally do not. Interestingly, a subset of MMRp CRCs contains variable fractions of MMRd cells, but it is unknown how their presence impacts immune surveillance. We asked whether modulation of the MMRd fraction in MMR heterogeneous tumors acts as an endogenous cancer vaccine by promoting immune surveillance. To test this hypothesis, we use isogenic MMRp (Mlh1+/+) and MMRd (Mlh1-/-) mouse CRC cells. MMRp/MMRd cells mixed at different ratios are injected in immunocompetent mice and tumor rejection is observed when at least 50% of cells are MMRd. To enrich the MMRd fraction, MMRp/MMRd tumors are treated with 6-thioguanine, which leads to tumor rejection. These results suggest that genetic and pharmacological modulation of the DNA mismatch repair machinery potentiate the immunogenicity of MMR heterogeneous tumors.

Published
2022

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