Bibliographic Details
| Title: |
TIM-3 Is a Potential Immune Checkpoint Target in Cats with Mammary Carcinoma. |
| Authors: |
Valente, Sofia1,2 (AUTHOR), Nascimento, Catarina1,2 (AUTHOR), Gameiro, Andreia1,2 (AUTHOR), Ferreira, João3 (AUTHOR), Correia, Jorge1,2 (AUTHOR), Ferreira, Fernando1,2 (AUTHOR) fernandof@fmv.ulisboa.pt |
| Source: |
Cancers. Jan2023, Vol. 15 Issue 2, p384. 15p. |
| Subject Terms: |
*IMMUNE checkpoint inhibitors, *GENETIC mutation, *ANIMAL experimentation, *IMMUNOHISTOCHEMISTRY, *CATS, *MEMBRANE glycoproteins, *TREATMENT effectiveness, *GENE expression, *ENZYME-linked immunosorbent assay, *DESCRIPTIVE statistics, *RESEARCH funding, *T cells, *TUMOR markers, *BREAST tumors, *IMMUNOTHERAPY, *PHARMACODYNAMICS |
| Abstract: |
Simple Summary: Feline mammary carcinomas are highly prevalent tumors, with aggressive behavior and scarce therapeutic options. Thus, there is a high need for novel biomarkers and therapeutic targets. In human medicine, immune checkpoint inhibitors targeting TIM-3 are emerging as promising treatment strategies; however, the clinical relevance of immune checkpoints in feline cancers is sparse. To unravel the clinical importance of TIM-3 in feline mammary carcinoma, we analyzed the intratumor expression and serum levels of the TIM-3 receptor in tumor-bearing cats. The results obtained show that TIM-3 is highly expressed in both immune and cancer cells, and the localization of TIM-3 expression can predict clinical outcomes in feline mammary carcinoma. TIM-3 levels in serum were reduced in diseased compared to healthy animals. These findings shed light on the biological role of TIM-3 in feline mammary carcinoma and support clinical testing of novel therapies targeting TIM-3. Recent findings in human breast cancer (HBC) indicate that T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM-3)-targeted therapies may effectively activate anticancer immune responses. Although feline mammary carcinoma (FMC) is a valuable cancer model, no studies on TIM-3 have been developed in this species. Thus, we evaluated the expression of TIM-3 by immunohistochemistry in total (t), stromal (s), and intra-tumoral (i) tumor-infiltrating lymphocytes (TILs) and in cancer cells, of 48 cats with mammary carcinoma. In parallel, serum TIM-3 levels were quantified using ELISA and the presence of somatic mutations in the TIM-3 gene was evaluated in 19 tumor samples. sTILs-TIM3+ were more frequent than iTILs-TIM-3+, with the TIM-3 ex-pression in sTILs and cancer cells being associated with more aggressive clinicopathological features. In contrast, the TIM-3 expression in iTILs and tTILs was associated with a more benign clinical course. Moreover, the serum TIM-3 levels were lower in animals with FMC when compared to healthy animals (p < 0.001). Only one somatic mutation was found in the TIM-3 gene, at intron 2, in one tumor sample. Altogether, our results suggest that the expression of TIM-3 among TILs subpopulations and cancer cells may influence the clinical outcome of cats with FMC, in line with the previous reports in HBC. [ABSTRACT FROM AUTHOR] |
|
Copyright of Cancers is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Academic Search Complete |
|
Full text is not displayed to guests. |
Login for full access.
|
