Izosimova Anna Vyacheslavovna, Shabalkina Alexandra Valerievna, Myshkin Mikhail Yurevich, Shurganova Elizaveta Viktorovna, Myalik Daria Sergeevna, Ryzhichenko Ekaterina Olegovna, Samitova Alina Faritovna, Barsova Ekaterina Vladimirovna, Shagina Irina Aleksandrovna, Britanova Olga Vladimirovna, Yuzhakova Diana Vladimirovna, Sharonov George Vladimirovich
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.
Vaccines (Basel). 2024 Mar 22;12(4):345. doi: 10.3390/vaccines12040345.
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.
一些肽类抗癌疫苗可引发强烈的T细胞记忆反应，但无法抑制肿瘤生长。为深入了解肿瘤抗性，我们比较了两种针对B16黑色素瘤的肽疫苗p20和p30，二者在体外均表现出良好的T细胞反应，但肿瘤抑制能力不同。
我们比较了两种肽疫苗在肿瘤引流淋巴结（dLN）和非引流淋巴结（ndLN）中T淋巴细胞的激活标志物和库。
我们发现，与p20疫苗相比，p30疫苗对肿瘤的控制效果更好。p20疫苗在体外诱导出更好的T细胞反应性，但未能抑制肿瘤生长。有效的抗肿瘤疫苗接种与dLN中细胞毒性T细胞（CTL）的更高克隆性相关，与ndLN相比，且大多数富集克隆会发生趋同。对于效果不佳的p20疫苗，扩增和趋同最多的是无淋巴结偏好的旁观者T细胞克隆。
在此，我们表明T细胞反应的克隆性和趋同是有效的抗肿瘤疫苗接种的标志。通过比较dLN和ndLN，可以避免这些参数的高度个体和方法依赖性。
