Tumor-infiltrating lymphocytes and immune-related adverse events in advanced melanoma
Background: The predictive value of tumor-infiltrating lymphocytes (TILs) in immune-related adverse event (irAE) development remains unknown, although an association between tumor immunogenicity and irAEs has been suggested. We investigated the association between TIL abundance in pretreatment prima...
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Elsevier
2024-12-01
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| Series: | Immuno-Oncology and Technology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S259001882400011X |
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| author | I.A.J. van Duin M. Schuiveling L.S. ter Maat M. Veta M.J.M. van Eijs R.J. Verheijden F.W.P.J. van den Berkmortel M.J. Boers-Sonderen G.A.P. Hospers M. Labots J.W.B. de Groot E. Kapiteijn D. Piersma G. Vreugdenhil H. Westgeest A.M.R. Schrader P.J. van Diest W.A.M. Blokx K.P.M. Suijkerbuijk |
| author_facet | I.A.J. van Duin M. Schuiveling L.S. ter Maat M. Veta M.J.M. van Eijs R.J. Verheijden F.W.P.J. van den Berkmortel M.J. Boers-Sonderen G.A.P. Hospers M. Labots J.W.B. de Groot E. Kapiteijn D. Piersma G. Vreugdenhil H. Westgeest A.M.R. Schrader P.J. van Diest W.A.M. Blokx K.P.M. Suijkerbuijk |
| author_sort | I.A.J. van Duin |
| collection | DOAJ |
| description | Background: The predictive value of tumor-infiltrating lymphocytes (TILs) in immune-related adverse event (irAE) development remains unknown, although an association between tumor immunogenicity and irAEs has been suggested. We investigated the association between TIL abundance in pretreatment primary and metastasis specimens and the subsequent development of severe irAEs. Patients and methods: We retrospectively identified patients with advanced cutaneous melanoma who received first-line anti-programmed cell death protein 1 (PD-1) with or without anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) from 10 hospitals in the Netherlands. TILs were scored on representative hematoxylin and eosin (H&E) stains of the primary melanoma and pretreatment melanoma metastasis as ‘absent’, ‘nonbrisk’, or ‘brisk’. A univariable logistic regression analysis was carried out to assess the association between the TIL scores and the development of severe irAEs. Fine and Gray subdistribution hazard models were used to estimate the cumulative incidence of severe irAEs. Results: Of the 1346 eligible patients, 536 patients had primary melanoma specimens available, and 613 patients had metastasis specimens available. Severe irAEs occurred in 15% of anti-PD-1-treated patients and 49% of anti-PD-1 + anti-CTLA-4-treated patients. The presence of TILs was not associated with the occurrence of grade ≥3 irAEs in primary melanoma specimens (P = 0.70) nor pretreatment metastasis specimens (P = 0.91). In the univariable analysis, patients with brisk TILs did not have a higher chance of developing severe irAEs compared with patients with absent TILs, for both primary specimen (odds ratio 1.15, 95% confidence interval 0.60-2.18) and metastasis specimen (odds ratio 0.77, 95% confidence interval 0.37-1.59). There was also no significant difference in the lifetime risk or timing of the development of severe irAEs in patients with TILs present compared with patients with TILs absent. Conclusion: There was no association between the TIL scores on H&E-stained slides from the primary melanoma or pretreatment metastasis and the development of grade 3 or higher irAEs. Additionally, no correlation was found between the presence of TILs and the timing of irAEs. |
| format | Article |
| id | doaj-art-d5af843cac4441619fbc2bc07a959fc8 |
| institution | Kabale University |
| issn | 2590-0188 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Immuno-Oncology and Technology |
| spelling | doaj-art-d5af843cac4441619fbc2bc07a959fc82024-12-19T10:56:49ZengElsevierImmuno-Oncology and Technology2590-01882024-12-0124100714Tumor-infiltrating lymphocytes and immune-related adverse events in advanced melanomaI.A.J. van Duin0M. Schuiveling1L.S. ter Maat2M. Veta3M.J.M. van Eijs4R.J. Verheijden5F.W.P.J. van den Berkmortel6M.J. Boers-Sonderen7G.A.P. Hospers8M. Labots9J.W.B. de Groot10E. Kapiteijn11D. Piersma12G. Vreugdenhil13H. Westgeest14A.M.R. Schrader15P.J. van Diest16W.A.M. Blokx17K.P.M. Suijkerbuijk18Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, UtrechtDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, UtrechtImage Sciences Institute, University Medical Center Utrecht, Utrecht University, UtrechtMedical Image Analysis, Department of Biomedical Engineering, Eindhoven University of Technology, EindhovenDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, UtrechtDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht; Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, UtrechtDepartment of Medical Oncology, Zuyderland Medical Centre, Sittard-GeleenDepartment of Medical Oncology, Radboud University Medical Centre, NijmegenDepartment of Medical Oncology, University Medical Centre Groningen, University of Groningen, GroningenDepartment of Medical Oncology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, AmsterdamIsala Oncology Center, Isala, ZwolleDepartment of Medical Oncology, Leiden University Medical Centre, LeidenDepartment of Internal Medicine, Medisch Spectrum Twente, EnschedeDepartment of Internal Medicine, Maxima Medical Centre, EindhovenDepartment of Internal Medicine, Amphia Hospital, BredaDepartment of Pathology, Leiden University Medical Centre, LeidenDepartment of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The NetherlandsDepartment of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The NetherlandsDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht; Correspondence to: Prof. Karijn P. M. Suijkerbuijk, Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, the NetherlandsBackground: The predictive value of tumor-infiltrating lymphocytes (TILs) in immune-related adverse event (irAE) development remains unknown, although an association between tumor immunogenicity and irAEs has been suggested. We investigated the association between TIL abundance in pretreatment primary and metastasis specimens and the subsequent development of severe irAEs. Patients and methods: We retrospectively identified patients with advanced cutaneous melanoma who received first-line anti-programmed cell death protein 1 (PD-1) with or without anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) from 10 hospitals in the Netherlands. TILs were scored on representative hematoxylin and eosin (H&E) stains of the primary melanoma and pretreatment melanoma metastasis as ‘absent’, ‘nonbrisk’, or ‘brisk’. A univariable logistic regression analysis was carried out to assess the association between the TIL scores and the development of severe irAEs. Fine and Gray subdistribution hazard models were used to estimate the cumulative incidence of severe irAEs. Results: Of the 1346 eligible patients, 536 patients had primary melanoma specimens available, and 613 patients had metastasis specimens available. Severe irAEs occurred in 15% of anti-PD-1-treated patients and 49% of anti-PD-1 + anti-CTLA-4-treated patients. The presence of TILs was not associated with the occurrence of grade ≥3 irAEs in primary melanoma specimens (P = 0.70) nor pretreatment metastasis specimens (P = 0.91). In the univariable analysis, patients with brisk TILs did not have a higher chance of developing severe irAEs compared with patients with absent TILs, for both primary specimen (odds ratio 1.15, 95% confidence interval 0.60-2.18) and metastasis specimen (odds ratio 0.77, 95% confidence interval 0.37-1.59). There was also no significant difference in the lifetime risk or timing of the development of severe irAEs in patients with TILs present compared with patients with TILs absent. Conclusion: There was no association between the TIL scores on H&E-stained slides from the primary melanoma or pretreatment metastasis and the development of grade 3 or higher irAEs. Additionally, no correlation was found between the presence of TILs and the timing of irAEs.http://www.sciencedirect.com/science/article/pii/S259001882400011Xmelanomaimmunotherapyimmune-related adverse eventspathologytumor-infiltrating lymphocytes |
| spellingShingle | I.A.J. van Duin M. Schuiveling L.S. ter Maat M. Veta M.J.M. van Eijs R.J. Verheijden F.W.P.J. van den Berkmortel M.J. Boers-Sonderen G.A.P. Hospers M. Labots J.W.B. de Groot E. Kapiteijn D. Piersma G. Vreugdenhil H. Westgeest A.M.R. Schrader P.J. van Diest W.A.M. Blokx K.P.M. Suijkerbuijk Tumor-infiltrating lymphocytes and immune-related adverse events in advanced melanoma Immuno-Oncology and Technology melanoma immunotherapy immune-related adverse events pathology tumor-infiltrating lymphocytes |
| title | Tumor-infiltrating lymphocytes and immune-related adverse events in advanced melanoma |
| title_full | Tumor-infiltrating lymphocytes and immune-related adverse events in advanced melanoma |
| title_fullStr | Tumor-infiltrating lymphocytes and immune-related adverse events in advanced melanoma |
| title_full_unstemmed | Tumor-infiltrating lymphocytes and immune-related adverse events in advanced melanoma |
| title_short | Tumor-infiltrating lymphocytes and immune-related adverse events in advanced melanoma |
| title_sort | tumor infiltrating lymphocytes and immune related adverse events in advanced melanoma |
| topic | melanoma immunotherapy immune-related adverse events pathology tumor-infiltrating lymphocytes |
| url | http://www.sciencedirect.com/science/article/pii/S259001882400011X |
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