{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:07:47Z","timestamp":1780096067595,"version":"3.54.0"},"reference-count":42,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RSF","award":["N\u00b025-75-30013"],"award-info":[{"award-number":["N\u00b025-75-30013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peptide vaccines possess several advantages over mRNA vaccines but are generally less effective at inducing antitumor immunity. The bottlenecks limiting peptide vaccine efficacy could be elucidated by tracking and comparing vaccine-induced T-lymphocytes in successful and unsuccessful cases. Here we have applied our recent database of neoantigen-specific T cell receptors (TCRs) to profile tumor-specific T cells following vaccination with a neoantigen peptide vaccine and to correlate this with the response. Mice were vaccinated prophylactically with p30 peptide encoding B16 melanoma neoantigen (K739N mutation in Kif18b gene). The B16F0 melanoma in the vaccinated mice was additionally treated by a CTLA-4 checkpoint blockade. T cells from the tumors, tumor-draining lymph nodes (tdLNs) and vaccine depots were isolated, phenotyped, sorted by subsets and sequenced for TCR repertoires. The vaccine induced the accumulation of tumor-specific CD4+ Th cells in the tdLNs, while in the tumors these cells were present and their frequencies were not changed by the vaccine. These cells also accumulated at the vaccine depots, where they were phenotypically skewed by the vaccine components; however, these effects were minor due to approximately 50-fold lower cell quantities compared to the tdLNs. Only some of the p30-specific Th cells showed tumoricidal activity, as revealed by the reverse correlation of their frequencies in the tdLNs with the tumor size. The CTLA-4 blockade did not affect the tumor growth or the frequencies of tumor-specific cells but did stimulate Th cell motility. Thus, we have shown that tumor-specific Th clones accumulate and\/or expand in the tdLNs, which correlates with tumor suppression but only for some of these clones. Tumor infiltration by these clones is not correlated with the growth rate.<\/jats:p>","DOI":"10.3390\/ijms26136453","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T08:58:23Z","timestamp":1751878703000},"page":"6453","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nodal Expansion, Tumor Infiltration and Exhaustion of Neoepitope-Specific Th Cells After Prophylactic Peptide Vaccination and Anti-CTLA4 Therapy in Mouse Melanoma B16"],"prefix":"10.3390","volume":"26","author":[{"given":"Alexandra V.","family":"Shabalkina","sequence":"first","affiliation":[{"name":"Research Institute of Translational Medicine, Pirogov Russian National Research Medical University, 1 Ostrovityanova, Moscow 117997, Russia"},{"name":"Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 16\/10 Miklukho-Maklaya, Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna V.","family":"Izosimova","sequence":"additional","affiliation":[{"name":"Research Institute of Experimental Oncology and Translational Biomedicine, Privolzhsky Research Medical University, 10\/1 Minin and Pozharsky Sq., Nizhny Novgorod 603950, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina O.","family":"Ryzhichenko","sequence":"additional","affiliation":[{"name":"Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 16\/10 Miklukho-Maklaya, Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizaveta V.","family":"Shurganova","sequence":"additional","affiliation":[{"name":"Research Institute of Experimental Oncology and Translational Biomedicine, Privolzhsky Research Medical University, 10\/1 Minin and Pozharsky Sq., Nizhny Novgorod 603950, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria S.","family":"Myalik","sequence":"additional","affiliation":[{"name":"Research Institute of Experimental Oncology and Translational Biomedicine, Privolzhsky Research Medical University, 10\/1 Minin and Pozharsky Sq., Nizhny Novgorod 603950, Russia"},{"name":"Pathoanatomical Department, Nizhny Novgorod Regional Clinical Cancer Hospital, Nizhny Novgorod 603126, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1448-132X","authenticated-orcid":false,"given":"Sofia V.","family":"Maryanchik","sequence":"additional","affiliation":[{"name":"Research Institute of Translational Medicine, Pirogov Russian National Research Medical University, 1 Ostrovityanova, Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria K.","family":"Ruppel","sequence":"additional","affiliation":[{"name":"Research Institute of Translational Medicine, Pirogov Russian National Research Medical University, 1 Ostrovityanova, Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitriy I.","family":"Knyazev","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, The University Clinic, Privolzhsky Research Medical University, 10\/1 Minin and Pozharsky Sq., Nizhny Novgorod 603950, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadezhda R.","family":"Khilal","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, The University Clinic, Privolzhsky Research Medical University, 10\/1 Minin and Pozharsky Sq., Nizhny Novgorod 603950, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina V.","family":"Barsova","sequence":"additional","affiliation":[{"name":"Research Institute of Translational Medicine, Pirogov Russian National Research Medical University, 1 Ostrovityanova, Moscow 117997, Russia"},{"name":"Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 16\/10 Miklukho-Maklaya, Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina A.","family":"Shagina","sequence":"additional","affiliation":[{"name":"Research Institute of Translational Medicine, Pirogov Russian National Research Medical University, 1 Ostrovityanova, Moscow 117997, Russia"},{"name":"Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 16\/10 Miklukho-Maklaya, Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George V.","family":"Sharonov","sequence":"additional","affiliation":[{"name":"Research Institute of Translational Medicine, Pirogov Russian National Research Medical University, 1 Ostrovityanova, Moscow 117997, Russia"},{"name":"Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 16\/10 Miklukho-Maklaya, Moscow 117997, Russia"},{"name":"Research Institute of Experimental Oncology and Translational Biomedicine, Privolzhsky Research Medical University, 10\/1 Minin and Pozharsky Sq., Nizhny Novgorod 603950, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1158\/0008-5472.CAN-11-3722","article-title":"Exploiting the Mutanome for Tumor Vaccination","volume":"72","author":"Castle","year":"2012","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nature14426","article-title":"Mutant MHC Class II Epitopes Drive Therapeutic Immune Responses to 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