TY - JOUR
T1 - Combination of chemotherapy and PD-1 blockade induces T cell responses to tumor non-mutated neoantigens
AU - Grimaldi, Alessio
AU - Cammarata, Ilenia
AU - Martire, Carmela
AU - Focaccetti, Chiara
AU - Piconese, Silvia
AU - Buccilli, Marta
AU - Mancone, Carmine
AU - Buzzacchino, Federica
AU - Berrios, Julio Rodrigo Giron
AU - D'Alessandris, Nicoletta
AU - Tomao, Silverio
AU - Giangaspero, Felice
AU - Paroli, Marino
AU - Caccavale, Rosalba
AU - Spinelli, Gian Paolo
AU - Girelli, Gabriella
AU - Peruzzi, Giovanna
AU - Nisticò, Paola
AU - Spada, Sheila
AU - Panetta, Mariangela
AU - Letizia Cecere, Fabiana
AU - Visca, Paolo
AU - Facciolo, Francesco
AU - Longo, Flavia
AU - Barnaba, Vincenzo
PY - 2020
Y1 - 2020
N2 - Here, we developed an unbiased, functional target-discovery platform to identify immunogenic proteins from primary non-small cell lung cancer (NSCLC) cells that had been induced to apoptosis by cisplatin (CDDP) treatment in vitro, as compared with their live counterparts. Among the multitude of proteins identified, some of them were represented as fragmented proteins in apoptotic tumor cells, and acted as non-mutated neoantigens (NM-neoAgs). Indeed, only the fragmented proteins elicited effective multi-specific CD4+ and CD8+ T cell responses, upon a chemotherapy protocol including CDDP. Importantly, these responses further increased upon anti-PD-1 therapy, and correlated with patients’ survival and decreased PD-1 expression. Cross-presentation assays showed that NM-neoAgs were unveiled in apoptotic tumor cells as the result of caspase-dependent proteolytic activity of cellular proteins. Our study demonstrates that apoptotic tumor cells generate a repertoire of immunogenic NM-neoAgs that could be potentially used for developing effective T cell-based immunotherapy across multiple cancer patients.
AB - Here, we developed an unbiased, functional target-discovery platform to identify immunogenic proteins from primary non-small cell lung cancer (NSCLC) cells that had been induced to apoptosis by cisplatin (CDDP) treatment in vitro, as compared with their live counterparts. Among the multitude of proteins identified, some of them were represented as fragmented proteins in apoptotic tumor cells, and acted as non-mutated neoantigens (NM-neoAgs). Indeed, only the fragmented proteins elicited effective multi-specific CD4+ and CD8+ T cell responses, upon a chemotherapy protocol including CDDP. Importantly, these responses further increased upon anti-PD-1 therapy, and correlated with patients’ survival and decreased PD-1 expression. Cross-presentation assays showed that NM-neoAgs were unveiled in apoptotic tumor cells as the result of caspase-dependent proteolytic activity of cellular proteins. Our study demonstrates that apoptotic tumor cells generate a repertoire of immunogenic NM-neoAgs that could be potentially used for developing effective T cell-based immunotherapy across multiple cancer patients.
KW - N/A
KW - N/A
UR - http://hdl.handle.net/10807/303811
U2 - 10.1038/s42003-020-0811-x
DO - 10.1038/s42003-020-0811-x
M3 - Article
SN - 2399-3642
VL - 3
SP - N/A-N/A
JO - Communications Biology
JF - Communications Biology
ER -