Corneal dendritic cells and the subbasal nerve plexus following neurotoxic treatment with oxaliplatin or paclitaxel

Jeremy Chung Bo Chiang; David Goldstein; Azadeh Tavakoli; Terry Trinh; Jacob Klisser; Craig R Lewis; Michael Friedlander; Thomas J Naduvilath; Kimberley Au; Susanna B Park; Arun V Krishnan; Maria Markoulli

doi:10.1038/s41598-021-02439-0

Corneal dendritic cells and the subbasal nerve plexus following neurotoxic treatment with oxaliplatin or paclitaxel

Jeremy Chung Bo Chiang^*, David Goldstein, Azadeh Tavakoli, Terry Trinh, Jacob Klisser, Craig R Lewis, Michael Friedlander, Thomas J Naduvilath, Kimberley Au, Susanna B Park, Arun V Krishnan, Maria Markoulli

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Immune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal microscopy. Corneal dendritic cell densities and nerve parameters in patients treated with neurotoxic chemotherapy were investigated. Patients treated for cancer with oxaliplatin (n = 39) or paclitaxel (n = 48), 3 to 24 months prior to assessment were recruited along with 40 healthy controls. Immature (ImDC), mature (MDC) and total dendritic cell densities (TotalDC), and corneal nerve parameters were analyzed from in-vivo corneal confocal microscopy images. ImDC was increased in the oxaliplatin group (Median, Md = 22.7 cells/mm 2) compared to healthy controls (Md = 10.1 cells/mm 2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm 2). ImDC was also associated with higher oxaliplatin cumulative dose (r = 0.33, p = 0.04) and treatment cycles (r = 0.40, p = 0.01). There was no significant difference in MDC between the three groups (p > 0.05). Corneal nerve parameters were reduced in both oxaliplatin and paclitaxel groups compared to healthy controls (p < 0.05). There is evidence of elevation of corneal ImDC in oxaliplatin-treated patients. Further investigation is required to explore this potential link through longitudinal studies and animal or laboratory-based immunohistochemical research.

Original language	English
Article number	22884
Number of pages	11
Journal	Scientific Reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-02439-0
Publication status	Published - 24 Nov 2021

Bibliographical note

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Keywords

Aged
Antineoplastic Agents/adverse effects
Case-Control Studies
Cornea/drug effects
Cross-Sectional Studies
Dendritic Cells/drug effects
Female
Humans
Male
Microscopy, Confocal
Middle Aged
Nerve Fibers/drug effects
Neurotoxicity Syndromes/etiology
Oxaliplatin/adverse effects
Paclitaxel/adverse effects
Time Factors
Treatment Outcome

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Chiangetal_2021_VoR
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Final published version, 1.63 MBLicence: CC BY 4.0

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Chiang, J. C. B., Goldstein, D., Tavakoli, A., Trinh, T., Klisser, J., Lewis, C. R., Friedlander, M., Naduvilath, T. J., Au, K., Park, S. B., Krishnan, A. V., & Markoulli, M. (2021). Corneal dendritic cells and the subbasal nerve plexus following neurotoxic treatment with oxaliplatin or paclitaxel. Scientific Reports, 11(1), Article 22884. https://doi.org/10.1038/s41598-021-02439-0

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abstract = "Immune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal microscopy. Corneal dendritic cell densities and nerve parameters in patients treated with neurotoxic chemotherapy were investigated. Patients treated for cancer with oxaliplatin (n = 39) or paclitaxel (n = 48), 3 to 24 months prior to assessment were recruited along with 40 healthy controls. Immature (ImDC), mature (MDC) and total dendritic cell densities (TotalDC), and corneal nerve parameters were analyzed from in-vivo corneal confocal microscopy images. ImDC was increased in the oxaliplatin group (Median, Md = 22.7 cells/mm 2) compared to healthy controls (Md = 10.1 cells/mm 2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm 2). ImDC was also associated with higher oxaliplatin cumulative dose (r = 0.33, p = 0.04) and treatment cycles (r = 0.40, p = 0.01). There was no significant difference in MDC between the three groups (p > 0.05). Corneal nerve parameters were reduced in both oxaliplatin and paclitaxel groups compared to healthy controls (p < 0.05). There is evidence of elevation of corneal ImDC in oxaliplatin-treated patients. Further investigation is required to explore this potential link through longitudinal studies and animal or laboratory-based immunohistochemical research. ",

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author = "Chiang, {Jeremy Chung Bo} and David Goldstein and Azadeh Tavakoli and Terry Trinh and Jacob Klisser and Lewis, {Craig R} and Michael Friedlander and Naduvilath, {Thomas J} and Kimberley Au and Park, {Susanna B} and Krishnan, {Arun V} and Maria Markoulli",

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AU - Chiang, Jeremy Chung Bo

AU - Goldstein, David

AU - Tavakoli, Azadeh

AU - Trinh, Terry

AU - Klisser, Jacob

AU - Lewis, Craig R

AU - Friedlander, Michael

AU - Naduvilath, Thomas J

AU - Au, Kimberley

AU - Park, Susanna B

AU - Krishnan, Arun V

AU - Markoulli, Maria

N1 - This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

PY - 2021/11/24

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N2 - Immune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal microscopy. Corneal dendritic cell densities and nerve parameters in patients treated with neurotoxic chemotherapy were investigated. Patients treated for cancer with oxaliplatin (n = 39) or paclitaxel (n = 48), 3 to 24 months prior to assessment were recruited along with 40 healthy controls. Immature (ImDC), mature (MDC) and total dendritic cell densities (TotalDC), and corneal nerve parameters were analyzed from in-vivo corneal confocal microscopy images. ImDC was increased in the oxaliplatin group (Median, Md = 22.7 cells/mm 2) compared to healthy controls (Md = 10.1 cells/mm 2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm 2). ImDC was also associated with higher oxaliplatin cumulative dose (r = 0.33, p = 0.04) and treatment cycles (r = 0.40, p = 0.01). There was no significant difference in MDC between the three groups (p > 0.05). Corneal nerve parameters were reduced in both oxaliplatin and paclitaxel groups compared to healthy controls (p < 0.05). There is evidence of elevation of corneal ImDC in oxaliplatin-treated patients. Further investigation is required to explore this potential link through longitudinal studies and animal or laboratory-based immunohistochemical research.

AB - Immune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal microscopy. Corneal dendritic cell densities and nerve parameters in patients treated with neurotoxic chemotherapy were investigated. Patients treated for cancer with oxaliplatin (n = 39) or paclitaxel (n = 48), 3 to 24 months prior to assessment were recruited along with 40 healthy controls. Immature (ImDC), mature (MDC) and total dendritic cell densities (TotalDC), and corneal nerve parameters were analyzed from in-vivo corneal confocal microscopy images. ImDC was increased in the oxaliplatin group (Median, Md = 22.7 cells/mm 2) compared to healthy controls (Md = 10.1 cells/mm 2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm 2). ImDC was also associated with higher oxaliplatin cumulative dose (r = 0.33, p = 0.04) and treatment cycles (r = 0.40, p = 0.01). There was no significant difference in MDC between the three groups (p > 0.05). Corneal nerve parameters were reduced in both oxaliplatin and paclitaxel groups compared to healthy controls (p < 0.05). There is evidence of elevation of corneal ImDC in oxaliplatin-treated patients. Further investigation is required to explore this potential link through longitudinal studies and animal or laboratory-based immunohistochemical research.

KW - Aged

KW - Antineoplastic Agents/adverse effects

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KW - Cornea/drug effects

KW - Cross-Sectional Studies

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KW - Female

KW - Humans

KW - Male

KW - Microscopy, Confocal

KW - Middle Aged

KW - Nerve Fibers/drug effects

KW - Neurotoxicity Syndromes/etiology

KW - Oxaliplatin/adverse effects

KW - Paclitaxel/adverse effects

KW - Time Factors

KW - Treatment Outcome

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DO - 10.1038/s41598-021-02439-0

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C2 - 34819589

SN - 2045-2322

VL - 11

JO - Scientific Reports

JF - Scientific Reports

IS - 1

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ER -

Corneal dendritic cells and the subbasal nerve plexus following neurotoxic treatment with oxaliplatin or paclitaxel

Abstract

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Keywords

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