Novel ocular immunotherapy induces tumor regression in an equine model of ocular surface squamous neoplasia

Wotman, Kathryn L.; Chow, Lyndah; Martabano, B. B.; Pezzanite, Lynn M.; Dow, Steven

doi:10.1007/s00262-022-03321-2

Cited by 2 publications

(2 citation statements)

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“…Risk factors for the development of OSSN include lack of periocular pigmentation, solar radiation exposure, heritable genetic mutations, acquired p53 mutations, physical periocular irritation, previous viral exposure, and potentially immunological and hormonal influences [4][5][6][7][8][9][10][11][12]. Although multiple treatment options have been described (e.g., surgical removal, intralesional chemotherapy, radiation therapy, cryotherapy, radiofrequency hyperthermia, immunotherapy, or combination), success rates vary widely (30 to 90%), and recurrence has been observed with all available treatment modalities [5,6,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Recently, however, the application of a novel liposomal immunotherapy has substantially improved OSSN treatment responses (including eyelid tumors) while minimizing local toxicity [27].…”

Section: Introductionmentioning

confidence: 99%

“…Although multiple treatment options have been described (e.g., surgical removal, intralesional chemotherapy, radiation therapy, cryotherapy, radiofrequency hyperthermia, immunotherapy, or combination), success rates vary widely (30 to 90%), and recurrence has been observed with all available treatment modalities [5,6,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Recently, however, the application of a novel liposomal immunotherapy has substantially improved OSSN treatment responses (including eyelid tumors) while minimizing local toxicity [27]. The ocular pathology of equine OSSN also presents several key similarities to that of OSSN in humans, including shared risk factors, lesion progression time, and similar gross and histologic appearances [1,9,10], further supporting the additional translational value of studies expanding our mechanistic understanding of OSSN disease processes in the equine model.…”

Section: Introductionmentioning

confidence: 99%

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Impact of Equine Ocular Surface Squamous Neoplasia on Interactions between Ocular Transcriptome and Microbiome

Chow,

Flaherty,

Pezzanite

et al. 2024

Veterinary Sciences

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Ocular surface squamous neoplasia (OSSN) represents the most common conjunctival tumor in horses and frequently results in vision loss and surgical removal of the affected globe. Multiple etiologic factors have been identified as contributing to OSSN progression, including solar radiation exposure, genetic mutations, and a lack of periocular pigmentation. Response to conventional treatments has been highly variable, though our recent work indicates that these tumors are highly responsive to local immunotherapy. In the present study, we extended our investigation of OSSN in horses to better understand how the ocular transcriptome responds to the presence of the tumor and how the ocular surface microbiome may also be altered by the presence of cancer. Therefore, we collected swabs from the ventral conjunctival fornix from 22 eyes in this study (11 with cytologically or histologically confirmed OSSN and 11 healthy eyes from the same horses) and performed RNA sequencing and 16S microbial sequencing using the same samples. Microbial 16s DNA sequencing and bulk RNA sequencing were both conducted using an Illumina-based platform. In eyes with OSSN, we observed significantly upregulated expression of genes and pathways associated with inflammation, particularly interferon. Microbial diversity was significantly reduced in conjunctival swabs from horses with OSSN. We also performed interactome analysis and found that three bacterial taxa (Actinobacillus, Helcococcus and Parvimona) had significant correlations with more than 100 upregulated genes in samples from animals with OSSN. These findings highlight the inflammatory nature of OSSN in horses and provide important new insights into how the host ocular surface interacts with certain microbial populations. These findings suggest new strategies for the management of OSSN in horses, which may entail immunotherapy in combination with ocular surface probiotics or prebiotics to help normalize ocular cell and microbe interactions.

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