Anti-ALK autoantibodies in patients with ALK-positive Non-Small Cell Lung Cancer (NSCLC): A monocentric experience
Importance: Deregulation of anaplastic lymphoma kinase (ALK) occurs in 3–7% of advanced NSCLC mainly because of chromosomic rearrangements at the ALK locus. Next to its oncogenic function, ALK chimeric oncoprotein is a possible antigen for human immune system. The prognostic value of natural anti-AL...
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2024-12-01
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| Series: | The Journal of Liquid Biopsy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950195424000298 |
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| author | Claudia Parisi José Carlos Benitez Hélène Lecourt Filippo Gustavo dall’Olio Mihaela Aldea Felix Blanc-Durand Véronique Vergé Cyril Quivoron Charles Naltet Pamela Abdayem Pernelle Lavaud Maria Rosa Ghigna Luc Friboulet Yohann Loriot Stéphane De Botton Vincent Ribrag Andrea Ardizzoni David Planchard Jean-Charles Soria Fabrice Barlesi Benjamin Besse |
| author_facet | Claudia Parisi José Carlos Benitez Hélène Lecourt Filippo Gustavo dall’Olio Mihaela Aldea Felix Blanc-Durand Véronique Vergé Cyril Quivoron Charles Naltet Pamela Abdayem Pernelle Lavaud Maria Rosa Ghigna Luc Friboulet Yohann Loriot Stéphane De Botton Vincent Ribrag Andrea Ardizzoni David Planchard Jean-Charles Soria Fabrice Barlesi Benjamin Besse |
| author_sort | Claudia Parisi |
| collection | DOAJ |
| description | Importance: Deregulation of anaplastic lymphoma kinase (ALK) occurs in 3–7% of advanced NSCLC mainly because of chromosomic rearrangements at the ALK locus. Next to its oncogenic function, ALK chimeric oncoprotein is a possible antigen for human immune system. The prognostic value of natural anti-ALK immunogenicity remains poorly explored in ALK + NSCLC. We hereby report preliminary results of a plasmatic anti-ALK a-abs titration assessment in a cohort of ALK + NSCLC pts. Objective: To evaluate the prevalence of pre-existing circulating anti-ALK a-abs in ALK + NSCLC pts. Key secondary objectives are the assessment of anti-ALK a-abs prognostic value and association with brain metastases (BM). Design: This monocentric case series included 60 ALK + NSCLC pts progressing on any anti-ALK TKIs between October 2015 and February 2021 at Gustave Roussy Cancer Campus. Fifty-six plasma samples were analyzed through a semiquantitative immunocytochemical technique. Plasma samples were obtained from two prospective studies approved by our Institutional Review Board: the MATCH-R trial (NCT02517892) and the MSN trial (RECF1256). Participants: We included pts diagnosed with unresectable stage III or IV NSCLC, either by contemporaneous or historical biopsy. ALK-rearrangement was identified by FISH, IHC or NGS. Pts were aged more than 18-year-old and had previously signed informed consent for one of the studies. Pts had received at least one anti-ALK-TKI during the disease history. Pts were not eligible if they had been diagnosed with a second cancer. Main outcomes and measures: The prevalence of plasmatic anti-ALK a-abs titer was reported as percentage. Progression-free survival, overall survival, and time to BM were analyzed using Kaplan-Meier methods. Results: We found an anti-ALK a-abs titer in 5 (9 %) pts. anti-ALK a-abs did not contribute to prolongation of survival. Although not significant, there was a trend towards protection against BM in the presence of anti-ALK a-abs. Conclusions and relevance: Because ALK fusion proteins are exclusively produced intracellularly, not all ALK autoantibodies may have direct anti-tumor impact with favorable prognostic value. This is the first investigation to explore the impact of circulating anti-ALK a-abs on BM. Prospective studies with longer follow-up are warranted to further explore the impact of anti-ALK a-abs on BM. |
| format | Article |
| id | doaj-art-31aa16d7e8e34c06b8453e1fba65c132 |
| institution | Kabale University |
| issn | 2950-1954 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | The Journal of Liquid Biopsy |
| spelling | doaj-art-31aa16d7e8e34c06b8453e1fba65c1322024-12-19T11:03:41ZengElsevierThe Journal of Liquid Biopsy2950-19542024-12-016100164Anti-ALK autoantibodies in patients with ALK-positive Non-Small Cell Lung Cancer (NSCLC): A monocentric experienceClaudia Parisi0José Carlos Benitez1Hélène Lecourt2Filippo Gustavo dall’Olio3Mihaela Aldea4Felix Blanc-Durand5Véronique Vergé6Cyril Quivoron7Charles Naltet8Pamela Abdayem9Pernelle Lavaud10Maria Rosa Ghigna11Luc Friboulet12Yohann Loriot13Stéphane De Botton14Vincent Ribrag15Andrea Ardizzoni16David Planchard17Jean-Charles Soria18Fabrice Barlesi19Benjamin Besse20Paris-Saclay University, Department of Cancer Medicine, Gustave Roussy, Villejuif, France; Department of Medical and Surgical Sciences and Translational Medicine, St Andrea University Hospital, Sapienza University, Rome, Italy; Corresponding author. 114 Rue Edouard Vaillant, 94805, Villejuif Cedex, France.University Hospital Virgen de la Victoria and Biomedical Research Institute of Malaga, MAlaga, SpainPTF AMMICa Recherche Translationnelle en Hématologie, Gustave Roussy, Villejuif, FranceParis-Saclay University, Department of Cancer Medicine, Gustave Roussy, Villejuif, FranceParis-Saclay University, Department of Cancer Medicine, Gustave Roussy, Villejuif, FranceParis-Saclay University, Department of Cancer Medicine, Gustave Roussy, Villejuif, FranceDepartment of Biology and Medical Pathology, Gustave Roussy, Villejuif, FrancePTF AMMICa Recherche Translationnelle en Hématologie, Gustave Roussy, Villejuif, FranceParis-Saclay University, Department of Cancer Medicine, Gustave Roussy, Villejuif, FranceParis-Saclay University, Department of Cancer Medicine, Gustave Roussy, Villejuif, FranceParis-Saclay University, Department of Cancer Medicine, Gustave Roussy, Villejuif, FranceDepartment of Laboratory Medicine and Pathology, Gustave Roussy, Villejuif, FranceINSERM U981, Gustave Roussy, Villejuif, FranceEarly Drug Development Department, Gustave Roussy, Villejuif, FranceHematology Department, Gustave Roussy, Villejuif, FranceHematology Department, Gustave Roussy, Villejuif, FranceIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyParis-Saclay University, Department of Cancer Medicine, Gustave Roussy, Villejuif, FranceParis-Saclay University, Department of Cancer Medicine, Gustave Roussy, Villejuif, FranceParis-Saclay University, Department of Cancer Medicine, Gustave Roussy, Villejuif, FranceParis-Saclay University, Department of Cancer Medicine, Gustave Roussy, Villejuif, FranceImportance: Deregulation of anaplastic lymphoma kinase (ALK) occurs in 3–7% of advanced NSCLC mainly because of chromosomic rearrangements at the ALK locus. Next to its oncogenic function, ALK chimeric oncoprotein is a possible antigen for human immune system. The prognostic value of natural anti-ALK immunogenicity remains poorly explored in ALK + NSCLC. We hereby report preliminary results of a plasmatic anti-ALK a-abs titration assessment in a cohort of ALK + NSCLC pts. Objective: To evaluate the prevalence of pre-existing circulating anti-ALK a-abs in ALK + NSCLC pts. Key secondary objectives are the assessment of anti-ALK a-abs prognostic value and association with brain metastases (BM). Design: This monocentric case series included 60 ALK + NSCLC pts progressing on any anti-ALK TKIs between October 2015 and February 2021 at Gustave Roussy Cancer Campus. Fifty-six plasma samples were analyzed through a semiquantitative immunocytochemical technique. Plasma samples were obtained from two prospective studies approved by our Institutional Review Board: the MATCH-R trial (NCT02517892) and the MSN trial (RECF1256). Participants: We included pts diagnosed with unresectable stage III or IV NSCLC, either by contemporaneous or historical biopsy. ALK-rearrangement was identified by FISH, IHC or NGS. Pts were aged more than 18-year-old and had previously signed informed consent for one of the studies. Pts had received at least one anti-ALK-TKI during the disease history. Pts were not eligible if they had been diagnosed with a second cancer. Main outcomes and measures: The prevalence of plasmatic anti-ALK a-abs titer was reported as percentage. Progression-free survival, overall survival, and time to BM were analyzed using Kaplan-Meier methods. Results: We found an anti-ALK a-abs titer in 5 (9 %) pts. anti-ALK a-abs did not contribute to prolongation of survival. Although not significant, there was a trend towards protection against BM in the presence of anti-ALK a-abs. Conclusions and relevance: Because ALK fusion proteins are exclusively produced intracellularly, not all ALK autoantibodies may have direct anti-tumor impact with favorable prognostic value. This is the first investigation to explore the impact of circulating anti-ALK a-abs on BM. Prospective studies with longer follow-up are warranted to further explore the impact of anti-ALK a-abs on BM.http://www.sciencedirect.com/science/article/pii/S2950195424000298Anaplastic lymphoma kinaseALKLung cancerNSCLCCirculating antibodiesImmunogenicity |
| spellingShingle | Claudia Parisi José Carlos Benitez Hélène Lecourt Filippo Gustavo dall’Olio Mihaela Aldea Felix Blanc-Durand Véronique Vergé Cyril Quivoron Charles Naltet Pamela Abdayem Pernelle Lavaud Maria Rosa Ghigna Luc Friboulet Yohann Loriot Stéphane De Botton Vincent Ribrag Andrea Ardizzoni David Planchard Jean-Charles Soria Fabrice Barlesi Benjamin Besse Anti-ALK autoantibodies in patients with ALK-positive Non-Small Cell Lung Cancer (NSCLC): A monocentric experience The Journal of Liquid Biopsy Anaplastic lymphoma kinase ALK Lung cancer NSCLC Circulating antibodies Immunogenicity |
| title | Anti-ALK autoantibodies in patients with ALK-positive Non-Small Cell Lung Cancer (NSCLC): A monocentric experience |
| title_full | Anti-ALK autoantibodies in patients with ALK-positive Non-Small Cell Lung Cancer (NSCLC): A monocentric experience |
| title_fullStr | Anti-ALK autoantibodies in patients with ALK-positive Non-Small Cell Lung Cancer (NSCLC): A monocentric experience |
| title_full_unstemmed | Anti-ALK autoantibodies in patients with ALK-positive Non-Small Cell Lung Cancer (NSCLC): A monocentric experience |
| title_short | Anti-ALK autoantibodies in patients with ALK-positive Non-Small Cell Lung Cancer (NSCLC): A monocentric experience |
| title_sort | anti alk autoantibodies in patients with alk positive non small cell lung cancer nsclc a monocentric experience |
| topic | Anaplastic lymphoma kinase ALK Lung cancer NSCLC Circulating antibodies Immunogenicity |
| url | http://www.sciencedirect.com/science/article/pii/S2950195424000298 |
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