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/mm2) compared to healthy controls (Md = 10.1 cells/mm2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm2). 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.
Highlights
Immune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment
There were more females in the paclitaxel group compared to the oxaliplatin group (χ = 27.31, df = 1, p < 0.001) and healthy controls (χ = 18.94, df = 1, p < 0.001) as paclitaxel is primarily used for treating breast and gynecological cancers
Our study investigated corneal neuroimmune features observed with in-vivo corneal confocal microscopy in patients who have completed treatment with neurotoxic chemotherapy with either paclitaxel or oxaliplatin
Summary
Immune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. Corneal confocal microscopy is a powerful instrument used in clinical research to observe microscopic changes in patients with both ocular and systemic pathologies peripheral neuropathic conditions[11,12] It is capable of non-invasive high-resolution imaging of small nerve fibers and resident immune cells, namely dendritic cells, in the subbasal nerve plexus of the cornea. While evidence of corneal nerve fiber loss has been shown with neurotoxic chemotherapy in both human and animal m odels[22,23], the changes in resident dendritic cells with chemotherapy have been limited to isolated case r eports[24] and the potential changes in treated patients across different major drug types remain unknown. The current study is novel in its investigation of in-vivo corneal dendritic cell densities and corneal nerve parameters in patients treated with oxaliplatin or paclitaxel. The second aim was to correlate these corneal neuroimmune features with the severity of peripheral neuropathy
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