Publications

Authors:

Balachandran, Vinod P; Łuksza, Marta; Zhao, Julia N; Makarov, Vladimir; Moral, John Alec; Remark, Romain; Herbst, Brian; Askan, Gokce; Bhanot, Umesh; Senbabaoglu, Yasin; Wells, Daniel K; Cary, Charles Ian Ormsby; Grbovic-huezo, Olivera; Attiyeh, Marc; Medina, Benjamin; Zhang, Jennifer; Loo, Jennifer; Saglimbeni, Joseph; Abu-akeel, Mohsen; Zappasodi, Roberta; Riaz, Nadeem; Smoragiewicz, Martin; Kelley, Z. Larkin; Basturk, Olca; Gönen, Mithat; Levine, Arnold J; Allen, Peter J; Fearon, Douglas T; Merad, Miriam; Gnjatic, Sacha; Iacobuzio-donahue, Christine A; Wolchok, Jedd D; Dematteo, Ronald P; Chan, Timothy A; Greenbaum, Benjamin D; Merghoub, Taha; Leach, Steven D; Johns, Al; Mead, Rs; Gill, Aj; Chang, Dk; Mckay, Sh; Chantrill, La; Chin, Vt; Chou, A; Humphris, Jl; Pajic, M; Steinmann, A; Arshi, M; Drury, A; Froio, D; Morgan, A; Timpson, P; Hermann, D; Vennin, C; Warren, S; Pinese, M; Wu, J; Pinho, Av; Mead, Rs; Tucker, K; Andrews, L; Gill, Aj; Samra, Js; Arena, J; Pavlakis, N; High, Ha; Mittal, A; Chang, Dk; Biankin, Av; Bailey, P; Martin, S; Musgrove, Ea; Jones, Md; Nourse, C; Jamieson, Nb; Chou, A; Chantrill, La; Stoita, A; Williams, D; Spigelman, A; Waddell, N; Pearson, Jv; Patch, Am; Nones, K; Newell, F; Mukhopadhyay, P; Addala, V; Kazakoff, S; Holmes, O; Leonard, C; Wood, S; Xu, C; Grimmond, Sm; Hofmann, O; Wilson, Pj; Christ, A; Bruxner, T; Asghari, R; Merrett, Nd; Pavey, D; Das, A; Goodwin, A; Cosman, Ph; Ismail, K; O'Connor, C; Cooper, Cl; Goodwin, A; Grimison, P; Kench, Jg; Sandroussi, C; Lam, Vw; Mcleod, D; Nagrial, Am; Kirk, J; James, V; Texler, M; Forest, C; Epari, Kp; Ballal, M; Fletcher, Dr; Mukhedkar, S; Zeps, N; Beilin, M; Feeney, K; Nguyen, Nq; Ruszkiewicz, Ar; Worthley, C; Chen, J; Brooke-Smith, Me; Papangelis, V; Clouston, Ad; Martin, P; Barbour, Ap; O'Rourke, Tj; Fawcett, Jw; Slater, K; Hatzifotis, M; Hodgkinson, P; Nikfarjam, M; Eshleman, Jr; Hruban, Rh; Wolfgang, Cl; Hodgin, M; Scarpa, A; Lawlor, Rt; Beghelli, S; Corbo, V; Scardoni, M; Bassi, C.

Title:

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Year:

2017

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

Nature

ISSN of journal:

0028-0836

N° Volume:

551

Number or Folder:

7681

Page numbers:

512-516

Keyword:

Pancreatic cancer, Translational immunology, Tumour immunology

Short description of contents:

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8(+) T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies.

Product ID:

101959

Handle IRIS:

11562/977179

Last Modified:

November 17, 2022

Bibliographic citation:

Balachandran, Vinod P; Łuksza, Marta; Zhao, Julia N; Makarov, Vladimir; Moral, John Alec; Remark, Romain; Herbst, Brian; Askan, Gokce; Bhanot, Umesh; Senbabaoglu, Yasin; Wells, Daniel K; Cary, Charles Ian Ormsby; Grbovic-huezo, Olivera; Attiyeh, Marc; Medina, Benjamin; Zhang, Jennifer; Loo, Jennifer; Saglimbeni, Joseph; Abu-akeel, Mohsen; Zappasodi, Roberta; Riaz, Nadeem; Smoragiewicz, Martin; Kelley, Z. Larkin; Basturk, Olca; Gönen, Mithat; Levine, Arnold J; Allen, Peter J; Fearon, Douglas T; Merad, Miriam; Gnjatic, Sacha; Iacobuzio-donahue, Christine A; Wolchok, Jedd D; Dematteo, Ronald P; Chan, Timothy A; Greenbaum, Benjamin D; Merghoub, Taha; Leach, Steven D; Johns, Al; Mead, Rs; Gill, Aj; Chang, Dk; Mckay, Sh; Chantrill, La; Chin, Vt; Chou, A; Humphris, Jl; Pajic, M; Steinmann, A; Arshi, M; Drury, A; Froio, D; Morgan, A; Timpson, P; Hermann, D; Vennin, C; Warren, S; Pinese, M; Wu, J; Pinho, Av; Mead, Rs; Tucker, K; Andrews, L; Gill, Aj; Samra, Js; Arena, J; Pavlakis, N; High, Ha; Mittal, A; Chang, Dk; Biankin, Av; Bailey, P; Martin, S; Musgrove, Ea; Jones, Md; Nourse, C; Jamieson, Nb; Chou, A; Chantrill, La; Stoita, A; Williams, D; Spigelman, A; Waddell, N; Pearson, Jv; Patch, Am; Nones, K; Newell, F; Mukhopadhyay, P; Addala, V; Kazakoff, S; Holmes, O; Leonard, C; Wood, S; Xu, C; Grimmond, Sm; Hofmann, O; Wilson, Pj; Christ, A; Bruxner, T; Asghari, R; Merrett, Nd; Pavey, D; Das, A; Goodwin, A; Cosman, Ph; Ismail, K; O'Connor, C; Cooper, Cl; Goodwin, A; Grimison, P; Kench, Jg; Sandroussi, C; Lam, Vw; Mcleod, D; Nagrial, Am; Kirk, J; James, V; Texler, M; Forest, C; Epari, Kp; Ballal, M; Fletcher, Dr; Mukhedkar, S; Zeps, N; Beilin, M; Feeney, K; Nguyen, Nq; Ruszkiewicz, Ar; Worthley, C; Chen, J; Brooke-Smith, Me; Papangelis, V; Clouston, Ad; Martin, P; Barbour, Ap; O'Rourke, Tj; Fawcett, Jw; Slater, K; Hatzifotis, M; Hodgkinson, P; Nikfarjam, M; Eshleman, Jr; Hruban, Rh; Wolfgang, Cl; Hodgin, M; Scarpa, A; Lawlor, Rt; Beghelli, S; Corbo, V; Scardoni, M; Bassi, C., Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer «Nature» , vol. 551 , n. 7681 , 2017 , pp. 512-516

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