Local Enrichment with Convergence of Enriched T-Cell Clones Are Hallmarks of Effective Peptide Vaccination against B16 Melanoma.

B16 melanoma TCR repertoire peptide anticancer vaccine

Journal

Vaccines
ISSN: 2076-393X
Titre abrégé: Vaccines (Basel)
Pays: Switzerland
ID NLM: 101629355

Informations de publication

Date de publication:
22 Mar 2024
Historique:
received: 16 01 2024
revised: 06 03 2024
accepted: 08 03 2024
medline: 27 4 2024
pubmed: 27 4 2024
entrez: 27 4 2024
Statut: epublish

Résumé

Some peptide anticancer vaccines elicit a strong T-cell memory response but fail to suppress tumor growth. To gain insight into tumor resistance, we compared two peptide vaccines, p20 and p30, against B16 melanoma, with both exhibiting good in vitro T-cell responses but different tumor suppression abilities. We compared activation markers and repertoires of T-lymphocytes from tumor-draining (dLN) and non-draining (ndLN) lymph nodes for the two peptide vaccines. We showed that the p30 vaccine had better tumor control as opposed to p20. p20 vaccine induced better in vitro T-cell responsiveness but failed to suppress tumor growth. Efficient antitumor vaccination is associated with a higher clonality of cytotoxic T-cells (CTLs) in dLNs compared with ndLNs and the convergence of most of the enriched clones. With the inefficient p20 vaccine, the most expanded and converged were clones of the bystander T-cells without an LN preference. Here, we show that the clonality and convergence of the T-cell response are the hallmarks of efficient antitumor vaccination. The high individual and methodological dependencies of these parameters can be avoided by comparing dLNs and ndLNs.

Sections du résumé

BACKGROUND BACKGROUND
Some peptide anticancer vaccines elicit a strong T-cell memory response but fail to suppress tumor growth. To gain insight into tumor resistance, we compared two peptide vaccines, p20 and p30, against B16 melanoma, with both exhibiting good in vitro T-cell responses but different tumor suppression abilities.
METHODS METHODS
We compared activation markers and repertoires of T-lymphocytes from tumor-draining (dLN) and non-draining (ndLN) lymph nodes for the two peptide vaccines.
RESULTS RESULTS
We showed that the p30 vaccine had better tumor control as opposed to p20. p20 vaccine induced better in vitro T-cell responsiveness but failed to suppress tumor growth. Efficient antitumor vaccination is associated with a higher clonality of cytotoxic T-cells (CTLs) in dLNs compared with ndLNs and the convergence of most of the enriched clones. With the inefficient p20 vaccine, the most expanded and converged were clones of the bystander T-cells without an LN preference.
CONCLUSIONS CONCLUSIONS
Here, we show that the clonality and convergence of the T-cell response are the hallmarks of efficient antitumor vaccination. The high individual and methodological dependencies of these parameters can be avoided by comparing dLNs and ndLNs.

Identifiants

pubmed: 38675728
pii: vaccines12040345
doi: 10.3390/vaccines12040345
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Russian Science Foundation
ID : 23-74-10109

Auteurs

Anna Vyacheslavovna Izosimova (AV)

Research Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod 603950, Russia.

Alexandra Valerievna Shabalkina (AV)

Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow 117997, Russia.
Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia.

Mikhail Yurevich Myshkin (MY)

Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia.

Elizaveta Viktorovna Shurganova (EV)

Research Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod 603950, Russia.

Daria Sergeevna Myalik (DS)

Research Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod 603950, Russia.
Pathoanatomical Department, Nizhny Novgorod Regional Clinical Cancer Hospital, Nizhny Novgorod 603126, Russia.

Ekaterina Olegovna Ryzhichenko (EO)

Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow 117997, Russia.

Alina Faritovna Samitova (AF)

Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow 117997, Russia.

Ekaterina Vladimirovna Barsova (EV)

Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow 117997, Russia.
Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia.

Irina Aleksandrovna Shagina (IA)

Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow 117997, Russia.
Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia.

Olga Vladimirovna Britanova (OV)

Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow 117997, Russia.
Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia.

Diana Vladimirovna Yuzhakova (DV)

Research Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod 603950, Russia.

George Vladimirovich Sharonov (GV)

Research Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod 603950, Russia.
Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow 117997, Russia.
Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia.

Classifications MeSH