EXPRESSION AND CLINICAL CORRELATION OF PD-1/PD-L1 AND VE1(BRAFP.V600E) IN PEDIATRIC LANGERHANS CELL HISTIOCYTOSIS
Main Article Content
Keywords
Langerhans cell histiocytosis, Paediatric, PD-1, PD-L1, VE1(BRAFp.V600E), Histiocytosis
Abstract
Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm with a wide spectrum of clinical presentations. Programmed Cell Death-1 (PD-1) receptor and its ligand (PD-L1) are overexpressed in LCH, but their clinical significance is unknown. We performed a clinical correlation study of PD-1/PD-L1 and VE1(BRAFp.V600E) expression in 131 children with LCH.
Methods: A total of 111 samples were tested for PD-1/PD-L1 and 109 for VE1(BRAFp.V600E) mutant protein by immunohistochemistry.
Results: PD-1, PD-L1 and VE1(BRAFp.V600E) positivity was observed in 40.5%, 31.53% and 55%, respectively. PD-1/ PD-L1 expression showed no significant effect on the rate of disease reactivations, early response to therapy or late sequelae. The 5-year EFS was not statistically different between patients with PD-1 positive compared to those with PD-1 negative tumours (47.7% vs.58.8%, p=0.17). Similar 5-year EFS rates were also seen in those who were PD-L1 positive compared to PD-L1 negative cases (50.5% vs.55.5%, p=0.61). VE1(BRAFp.V600E) positivity was associated with a significantly higher frequency of risk-organ involvement (p=0.0053), but no significant effect on early response to therapy or rates of reactivations or late sequelae.
Conclusions: Our study showed no significant correlation between VE1(BRAFp.V600E) expression, PD-1 and PD-L1 a clinical outcome in pediatric LCH.
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3. Fernandez LF, Menor SF, Alonso CS, Arenas JJ. Langerhans cell histiocytosis of the temporal bone in paediatric patients. Am J Roentgenol.2000; 174:217-21.
4. Gadner H, Grois N, Potschger U, et al. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood.2008;111:2556-62.
5. Gadner H, Grois N, Potschger U, Minkov M,Arico M, Braier J,Broadbent V, Donadieu J, Henter JI, McCarter R,Ladisch S, Histiocyte society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood.2013;121:5006-5014.
6. Haupt R, Nanduri V, Calevo MG, Bernstrand C, Braier JL, Broadbent V, Rey G, McClain KL., Schaub J, Egeler RM. Permanent consequences in Langerhans cell histiocytosis patients. A pilot study from the Histiocytic Society-Late Effects Study Group. Pediatr Blood Cancer.2004;42:438-444.
7. Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brander B, Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, Kuo FC, Ligon AH, Stevenson KE, Kehoe SM, Garraway LA, Hahn WC, Meyerson M, Fleming MD, Rollins BJ. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 2010 Sep 16;116(11):1919-23. doi: 10.1182/blood-2010-04-279083. Epub 2010 Jun 2. PMID: 20519626; PMCID: PMC3173987.
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12. Abla O, Weitzman S. Treatment of Langerhans cell histiocytosis: role of BRAF/MAPK inhibition. Hematology Am Hematol Educ Program. 2015:565-570.
13. Allen CE, Li L, Peters TL, Leung HC, Yu A, Man TK, Gurusiddappa S, Phillips MT, Hicks MJ, Gaikwad A, Merad M, McClain KL. Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells. J Immunol. 2010 Apr 15;184(8):4557-67. doi: 10.4049/jimmunol.0902336. Epub 2010 Mar 10. PMID: 20220088; PMCID: PMC3142675.
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16. Sengal A, Velazquez J, Hahne M, Burke TM, Abhyankar H, Reyes R, Olea W, Scull B, Eckstein OS, Bigenwald C, Bollard CM, Yu W, Merad M, McClain KL, Allen CE, Chakraborty R. Overcoming T-cell exhaustion in LCH: PD-1 blockade and targeted MAPK inhibition are synergistic in a mouse model of LCH. Blood. 2021 Apr 1;137(13):1777-1791. doi: 10.1182/blood.2020005867. PMID: 33075814; PMCID: PMC8020265.
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18. Eckstein OS, Visser J, Rodriguez-Galindo C, Allen CE; NACHO-LIBRE Study Group. Clinical responses and persistent BRAF V600E+ blood cells in children with LCH treated with MAPK pathway inhibition. Blood. 2019 Apr 11;133(15):1691-1694. doi: 10.1182/blood-2018-10-878363. Epub 2019 Feb 4. PMID: 30718231; PMCID: PMC6460419.
19. Leslie C, Bowyer SE, White A, Grieu-Iacopetta F, Trevenen M, Iacopetta B, Amanuel B, Millward M. FOXP3+ T regulatory lymphocytes in primary melanoma are associated with BRAF mutation but not with response to BRAF inhibitor. Pathology. 2015 Oct;47(6):557-63. doi: 10.1097/PAT.0000000000000314. PMID: 26308130.
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Apr 27, 2023
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tandon, sneha (2023) “EXPRESSION AND CLINICAL CORRELATION OF PD-1/PD-L1 AND VE1(BRAFP.V600E) IN PEDIATRIC LANGERHANS CELL HISTIOCYTOSIS ”, Mediterranean Journal of Hematology and Infectious Diseases, 15(1), p. e2023035. doi: 10.4084/MJHID.2023.035.
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