Peripheral T cell receptor repertoire features predict durable responses to anti-PD-1 inhibitor monotherapy in advanced renal cell carcinoma
Immune checkpoint inhibitors (ICIs) offer significant clinical benefits to a subset of cancer patients via the induction of a systemic T cell-mediated anti-cancer immune response. Thus, the dynamic characterization of T cell repertoires in the peripheral blood has the potential to demonstrate noninv...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-01-01
|
| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2020.1862948 |
| _version_ | 1798034039666376704 |
|---|---|
| author | Taigo Kato Kazuma Kiyotani Eisuke Tomiyama Yoko Koh Makoto Matsushita Yujiro Hayashi Kosuke Nakano Yu Ishizuya Cong Wang Koji Hatano Atsunari Kawashima Takeshi Ujike Kazutoshi Fujita Norio Nonomura Motohide Uemura |
| author_facet | Taigo Kato Kazuma Kiyotani Eisuke Tomiyama Yoko Koh Makoto Matsushita Yujiro Hayashi Kosuke Nakano Yu Ishizuya Cong Wang Koji Hatano Atsunari Kawashima Takeshi Ujike Kazutoshi Fujita Norio Nonomura Motohide Uemura |
| author_sort | Taigo Kato |
| collection | DOAJ |
| description | Immune checkpoint inhibitors (ICIs) offer significant clinical benefits to a subset of cancer patients via the induction of a systemic T cell-mediated anti-cancer immune response. Thus, the dynamic characterization of T cell repertoires in the peripheral blood has the potential to demonstrate noninvasive predictive biomarkers for the clinical efficacy of ICIs. In this study, we collected tumor tissues and peripheral blood samples from 25 patients with advanced kidney cancer before anti-programmed cell death protein 1 (PD-1) treatment and 1, 3, and 6 months after treatment initiation. Furthermore, we applied a next-generation sequencing approach to characterize T cell receptor (TCR) alpha and beta repertoires. TCR repertoire analysis revealed that the responders to anti-PD-1 showed an expansion of certain T cell clones even in the blood, as evidenced by the significant decrease in the TCR diversity index and increase in the number of expanded TCR clonotypes 1 month after treatment. Interestingly, these expanded TCR clonotypes in the peripheral blood were significantly shared with tumor-infiltrating T cells in responders, indicating that they have many circulating T cells that may recognize cancer antigens. Expression analysis also revealed that 1 month after treatment, T cells from the peripheral blood of responders showed significantly elevated transcriptional levels of Granzyme B, Perforin, CD39, and PD-1, markers of cancer-associated antigen-specific T cells. Altogether, we propose that global TCR repertoire analysis may allow identifying early surrogate biomarkers in the peripheral blood for predicting clinical responses to anti-PD-1 monotherapy. |
| first_indexed | 2024-04-11T20:38:41Z |
| format | Article |
| id | doaj.art-3a55cca753ff46178554323903ba69b8 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-04-11T20:38:41Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-3a55cca753ff46178554323903ba69b82022-12-22T04:04:17ZengTaylor & Francis GroupOncoImmunology2162-402X2021-01-0110110.1080/2162402X.2020.18629481862948Peripheral T cell receptor repertoire features predict durable responses to anti-PD-1 inhibitor monotherapy in advanced renal cell carcinomaTaigo Kato0Kazuma Kiyotani1Eisuke Tomiyama2Yoko Koh3Makoto Matsushita4Yujiro Hayashi5Kosuke Nakano6Yu Ishizuya7Cong Wang8Koji Hatano9Atsunari Kawashima10Takeshi Ujike11Kazutoshi Fujita12Norio Nonomura13Motohide Uemura14Osaka University Graduate School of MedicineJapanese Foundation for Cancer ResearchOsaka University Graduate School of MedicineOsaka University Graduate School of MedicineOsaka University Graduate School of MedicineOsaka University Graduate School of MedicineOsaka University Graduate School of MedicineOsaka University Graduate School of MedicineOsaka University Graduate School of MedicineOsaka University Graduate School of MedicineOsaka University Graduate School of MedicineOsaka University Graduate School of MedicineOsaka University Graduate School of MedicineOsaka University Graduate School of MedicineOsaka University Graduate School of MedicineImmune checkpoint inhibitors (ICIs) offer significant clinical benefits to a subset of cancer patients via the induction of a systemic T cell-mediated anti-cancer immune response. Thus, the dynamic characterization of T cell repertoires in the peripheral blood has the potential to demonstrate noninvasive predictive biomarkers for the clinical efficacy of ICIs. In this study, we collected tumor tissues and peripheral blood samples from 25 patients with advanced kidney cancer before anti-programmed cell death protein 1 (PD-1) treatment and 1, 3, and 6 months after treatment initiation. Furthermore, we applied a next-generation sequencing approach to characterize T cell receptor (TCR) alpha and beta repertoires. TCR repertoire analysis revealed that the responders to anti-PD-1 showed an expansion of certain T cell clones even in the blood, as evidenced by the significant decrease in the TCR diversity index and increase in the number of expanded TCR clonotypes 1 month after treatment. Interestingly, these expanded TCR clonotypes in the peripheral blood were significantly shared with tumor-infiltrating T cells in responders, indicating that they have many circulating T cells that may recognize cancer antigens. Expression analysis also revealed that 1 month after treatment, T cells from the peripheral blood of responders showed significantly elevated transcriptional levels of Granzyme B, Perforin, CD39, and PD-1, markers of cancer-associated antigen-specific T cells. Altogether, we propose that global TCR repertoire analysis may allow identifying early surrogate biomarkers in the peripheral blood for predicting clinical responses to anti-PD-1 monotherapy.http://dx.doi.org/10.1080/2162402X.2020.1862948immune checkpoint inhibitorspredictive markert cell receptorrenal cell carcinomanext-generation sequencing |
| spellingShingle | Taigo Kato Kazuma Kiyotani Eisuke Tomiyama Yoko Koh Makoto Matsushita Yujiro Hayashi Kosuke Nakano Yu Ishizuya Cong Wang Koji Hatano Atsunari Kawashima Takeshi Ujike Kazutoshi Fujita Norio Nonomura Motohide Uemura Peripheral T cell receptor repertoire features predict durable responses to anti-PD-1 inhibitor monotherapy in advanced renal cell carcinoma OncoImmunology immune checkpoint inhibitors predictive marker t cell receptor renal cell carcinoma next-generation sequencing |
| title | Peripheral T cell receptor repertoire features predict durable responses to anti-PD-1 inhibitor monotherapy in advanced renal cell carcinoma |
| title_full | Peripheral T cell receptor repertoire features predict durable responses to anti-PD-1 inhibitor monotherapy in advanced renal cell carcinoma |
| title_fullStr | Peripheral T cell receptor repertoire features predict durable responses to anti-PD-1 inhibitor monotherapy in advanced renal cell carcinoma |
| title_full_unstemmed | Peripheral T cell receptor repertoire features predict durable responses to anti-PD-1 inhibitor monotherapy in advanced renal cell carcinoma |
| title_short | Peripheral T cell receptor repertoire features predict durable responses to anti-PD-1 inhibitor monotherapy in advanced renal cell carcinoma |
| title_sort | peripheral t cell receptor repertoire features predict durable responses to anti pd 1 inhibitor monotherapy in advanced renal cell carcinoma |
| topic | immune checkpoint inhibitors predictive marker t cell receptor renal cell carcinoma next-generation sequencing |
| url | http://dx.doi.org/10.1080/2162402X.2020.1862948 |
| work_keys_str_mv | AT taigokato peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT kazumakiyotani peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT eisuketomiyama peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT yokokoh peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT makotomatsushita peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT yujirohayashi peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT kosukenakano peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT yuishizuya peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT congwang peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT kojihatano peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT atsunarikawashima peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT takeshiujike peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT kazutoshifujita peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT noriononomura peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma AT motohideuemura peripheraltcellreceptorrepertoirefeaturespredictdurableresponsestoantipd1inhibitormonotherapyinadvancedrenalcellcarcinoma |