Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell Dynamics
Hyperprogressive disease (HPD) is an adverse outcome of immunotherapy consisting of an acceleration of tumor growth associated with prompt clinical deterioration. The definitions based on radiological evaluation present important technical limitations. No biomarkers have been identified yet. In this...
| Autores: | , , , , , , , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Recursos: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/66188 |
| Acesso em linha: | https://hdl.handle.net/10171/66188 |
| Access Level: | acceso abierto |
| Palavra-chave: | Hyperprogressive disease Immunotherapy NSCLC |
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Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell DynamicsArasanz, H. (Hugo)|||/items/af58f0cb-4fe5-409c-a96a-b2a6b6831b48Zuazo, M. (Miren)|||/items/b3adff74-ba07-454d-a65b-1c19349daa54Bocanegra, A. (Ana)|||/items/bb0c2c14-2f4e-4fcb-a6de-a1268735f4cdGato-Cañas, M. (María)|||/items/ed21e1d0-319e-4b1c-a1f5-2c1be4560659Martinez-Aguillo, M. (M.)|||/items/1a956353-bfc8-4100-896e-781680752477Morilla, I. (Idoia)|||/items/c84da7a6-e847-47d6-9923-e5835fb0ae43Fernández-Hinojal, G. (Gonzalo)|||/items/6a8e64fe-0006-4d63-885f-3c030209f545Hernández, B. (Berta)|||/items/af86bb89-779a-4967-b8fe-328660ef3211López, P. (Paúl)|||/items/8db63426-ae56-4987-8d33-e80641262ffeAlberdi, N. (Nerea)|||/items/6769755c-4df3-406a-8f3e-c18da78e8b77Hernández, C. (Carlos)|||/items/68e53601-57fa-4c2b-b8cd-70a92647b1f7Chocarro, L. (Luisa)|||/items/6f7649fe-4d5c-4596-8bff-0a4c4797e891Teijeira, L. (Lucía)|||/items/adae94b4-a30a-4c57-a728-ca13bfe3f0b6Vera, R. (Ruth)|||/items/c5e822da-e29b-4f65-bb1c-be8bb5b999e1Kochan, G. (Grazyna)|||/items/bf76a215-0675-467b-bb79-f2b4192fa4b2Escors, D. (David)|||/items/82737dd6-3010-4c11-ae0f-a6efb4f177a6Hyperprogressive diseaseImmunotherapyNSCLCHyperprogressive disease (HPD) is an adverse outcome of immunotherapy consisting of an acceleration of tumor growth associated with prompt clinical deterioration. The definitions based on radiological evaluation present important technical limitations. No biomarkers have been identified yet. In this study, 70 metastatic NSCLC patients treated with anti-PD-1/PD-L1 immunotherapy after progression to platinum-based therapy were prospectively studied. Samples from peripheral blood were obtained before the first (baseline) and second cycles of treatment. Peripheral blood mononuclear cells (PBMCs) were isolated and differentiation stages of CD4 lymphocytes quantified by flow cytometry and correlated with HPD as identified with radiological criteria. A strong expansion of highly differentiated CD28− CD4 T lymphocytes (CD4 THD) between the first and second cycle of therapy was observed in HPD patients. After normalizing, the proportion of posttreatment/pretreatment CD4 THD was significantly higher in HPD when compared with the rest of patients (median 1.525 vs. 0.990; p = 0.0007), and also when stratifying by HPD, non-HPD progressors, and responders (1.525, 1.000 and 0.9700 respectively; p = 0.0025). A cut-off value of 1.3 identified HPD with 82% specificity and 70% sensitivity. An increase of CD28− CD4 T lymphocytes ≥ 1.3 (CD4 THD burst) was significantly associated with HPD (p = 0.008). The tumor growth ratio (TGR) was significantly higher in patients with expansion of CD4 THD burst compared to the rest of patients (median 2.67 vs. 0.86, p = 0.0049), and also when considering only progressors (median 2.67 vs. 1.03, p = 0.0126). A strong expansion of CD28− CD4 lymphocytes in peripheral blood within the first cycle of therapy is an early differential feature of HPD in NSCLC treated with immune-checkpoint inhibitors. The monitoring of T cell dynamics allows the early detection of this adverse outcome in clinical practice and complements radiological evaluation.Dadun. Depósito Académico Digital Universidad de Navarra20232023-05-0520202020-01-0120202020-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/66188reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/661882026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell Dynamics |
| title |
Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell Dynamics |
| spellingShingle |
Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell Dynamics Arasanz, H. (Hugo)|||/items/af58f0cb-4fe5-409c-a96a-b2a6b6831b48 Hyperprogressive disease Immunotherapy NSCLC |
| title_short |
Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell Dynamics |
| title_full |
Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell Dynamics |
| title_fullStr |
Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell Dynamics |
| title_full_unstemmed |
Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell Dynamics |
| title_sort |
Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell Dynamics |
| dc.creator.none.fl_str_mv |
Arasanz, H. (Hugo)|||/items/af58f0cb-4fe5-409c-a96a-b2a6b6831b48 Zuazo, M. (Miren)|||/items/b3adff74-ba07-454d-a65b-1c19349daa54 Bocanegra, A. (Ana)|||/items/bb0c2c14-2f4e-4fcb-a6de-a1268735f4cd Gato-Cañas, M. (María)|||/items/ed21e1d0-319e-4b1c-a1f5-2c1be4560659 Martinez-Aguillo, M. (M.)|||/items/1a956353-bfc8-4100-896e-781680752477 Morilla, I. (Idoia)|||/items/c84da7a6-e847-47d6-9923-e5835fb0ae43 Fernández-Hinojal, G. (Gonzalo)|||/items/6a8e64fe-0006-4d63-885f-3c030209f545 Hernández, B. (Berta)|||/items/af86bb89-779a-4967-b8fe-328660ef3211 López, P. (Paúl)|||/items/8db63426-ae56-4987-8d33-e80641262ffe Alberdi, N. (Nerea)|||/items/6769755c-4df3-406a-8f3e-c18da78e8b77 Hernández, C. (Carlos)|||/items/68e53601-57fa-4c2b-b8cd-70a92647b1f7 Chocarro, L. (Luisa)|||/items/6f7649fe-4d5c-4596-8bff-0a4c4797e891 Teijeira, L. (Lucía)|||/items/adae94b4-a30a-4c57-a728-ca13bfe3f0b6 Vera, R. (Ruth)|||/items/c5e822da-e29b-4f65-bb1c-be8bb5b999e1 Kochan, G. (Grazyna)|||/items/bf76a215-0675-467b-bb79-f2b4192fa4b2 Escors, D. (David)|||/items/82737dd6-3010-4c11-ae0f-a6efb4f177a6 |
| author |
Arasanz, H. (Hugo)|||/items/af58f0cb-4fe5-409c-a96a-b2a6b6831b48 |
| author_facet |
Arasanz, H. (Hugo)|||/items/af58f0cb-4fe5-409c-a96a-b2a6b6831b48 Zuazo, M. (Miren)|||/items/b3adff74-ba07-454d-a65b-1c19349daa54 Bocanegra, A. (Ana)|||/items/bb0c2c14-2f4e-4fcb-a6de-a1268735f4cd Gato-Cañas, M. (María)|||/items/ed21e1d0-319e-4b1c-a1f5-2c1be4560659 Martinez-Aguillo, M. (M.)|||/items/1a956353-bfc8-4100-896e-781680752477 Morilla, I. (Idoia)|||/items/c84da7a6-e847-47d6-9923-e5835fb0ae43 Fernández-Hinojal, G. (Gonzalo)|||/items/6a8e64fe-0006-4d63-885f-3c030209f545 Hernández, B. (Berta)|||/items/af86bb89-779a-4967-b8fe-328660ef3211 López, P. (Paúl)|||/items/8db63426-ae56-4987-8d33-e80641262ffe Alberdi, N. (Nerea)|||/items/6769755c-4df3-406a-8f3e-c18da78e8b77 Hernández, C. (Carlos)|||/items/68e53601-57fa-4c2b-b8cd-70a92647b1f7 Chocarro, L. (Luisa)|||/items/6f7649fe-4d5c-4596-8bff-0a4c4797e891 Teijeira, L. (Lucía)|||/items/adae94b4-a30a-4c57-a728-ca13bfe3f0b6 Vera, R. (Ruth)|||/items/c5e822da-e29b-4f65-bb1c-be8bb5b999e1 Kochan, G. (Grazyna)|||/items/bf76a215-0675-467b-bb79-f2b4192fa4b2 Escors, D. (David)|||/items/82737dd6-3010-4c11-ae0f-a6efb4f177a6 |
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author |
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Zuazo, M. (Miren)|||/items/b3adff74-ba07-454d-a65b-1c19349daa54 Bocanegra, A. (Ana)|||/items/bb0c2c14-2f4e-4fcb-a6de-a1268735f4cd Gato-Cañas, M. (María)|||/items/ed21e1d0-319e-4b1c-a1f5-2c1be4560659 Martinez-Aguillo, M. (M.)|||/items/1a956353-bfc8-4100-896e-781680752477 Morilla, I. (Idoia)|||/items/c84da7a6-e847-47d6-9923-e5835fb0ae43 Fernández-Hinojal, G. (Gonzalo)|||/items/6a8e64fe-0006-4d63-885f-3c030209f545 Hernández, B. (Berta)|||/items/af86bb89-779a-4967-b8fe-328660ef3211 López, P. (Paúl)|||/items/8db63426-ae56-4987-8d33-e80641262ffe Alberdi, N. (Nerea)|||/items/6769755c-4df3-406a-8f3e-c18da78e8b77 Hernández, C. (Carlos)|||/items/68e53601-57fa-4c2b-b8cd-70a92647b1f7 Chocarro, L. (Luisa)|||/items/6f7649fe-4d5c-4596-8bff-0a4c4797e891 Teijeira, L. (Lucía)|||/items/adae94b4-a30a-4c57-a728-ca13bfe3f0b6 Vera, R. (Ruth)|||/items/c5e822da-e29b-4f65-bb1c-be8bb5b999e1 Kochan, G. (Grazyna)|||/items/bf76a215-0675-467b-bb79-f2b4192fa4b2 Escors, D. (David)|||/items/82737dd6-3010-4c11-ae0f-a6efb4f177a6 |
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author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Hyperprogressive disease Immunotherapy NSCLC |
| topic |
Hyperprogressive disease Immunotherapy NSCLC |
| description |
Hyperprogressive disease (HPD) is an adverse outcome of immunotherapy consisting of an acceleration of tumor growth associated with prompt clinical deterioration. The definitions based on radiological evaluation present important technical limitations. No biomarkers have been identified yet. In this study, 70 metastatic NSCLC patients treated with anti-PD-1/PD-L1 immunotherapy after progression to platinum-based therapy were prospectively studied. Samples from peripheral blood were obtained before the first (baseline) and second cycles of treatment. Peripheral blood mononuclear cells (PBMCs) were isolated and differentiation stages of CD4 lymphocytes quantified by flow cytometry and correlated with HPD as identified with radiological criteria. A strong expansion of highly differentiated CD28− CD4 T lymphocytes (CD4 THD) between the first and second cycle of therapy was observed in HPD patients. After normalizing, the proportion of posttreatment/pretreatment CD4 THD was significantly higher in HPD when compared with the rest of patients (median 1.525 vs. 0.990; p = 0.0007), and also when stratifying by HPD, non-HPD progressors, and responders (1.525, 1.000 and 0.9700 respectively; p = 0.0025). A cut-off value of 1.3 identified HPD with 82% specificity and 70% sensitivity. An increase of CD28− CD4 T lymphocytes ≥ 1.3 (CD4 THD burst) was significantly associated with HPD (p = 0.008). The tumor growth ratio (TGR) was significantly higher in patients with expansion of CD4 THD burst compared to the rest of patients (median 2.67 vs. 0.86, p = 0.0049), and also when considering only progressors (median 2.67 vs. 1.03, p = 0.0126). A strong expansion of CD28− CD4 lymphocytes in peripheral blood within the first cycle of therapy is an early differential feature of HPD in NSCLC treated with immune-checkpoint inhibitors. The monitoring of T cell dynamics allows the early detection of this adverse outcome in clinical practice and complements radiological evaluation. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-01-01 2020 2020-01-01 2023 2023-05-05 |
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journal article http://purl.org/coar/resource_type/c_6501 |
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info:eu-repo/semantics/article |
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article |
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https://hdl.handle.net/10171/66188 |
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https://hdl.handle.net/10171/66188 |
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Inglés eng |
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Inglés |
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eng |
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open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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