Abstract 3207: TIM-3 expression in human cancer: A tissue microarray study on 17,172 patients

Abstract TIM-3 (T-cell immunoglobulin and mucin-domain containing-3) is an inhibitory immune checkpoint molecule which mainly occurs in subsets of inflammatory cells. On the surface membrane of cancer cells TIM-3 may represent a druggable target. To assess the prevalence of TIM-3 expression in cancer, a tissue microarray containing 17, 172 samples from 134 different tumor types and subtypes was analyzed by immunohistochemistry (IHC). TIM-3 expression of tumor cells and macrophages were semiquantitatively recorded. In cancer cells, a membranous TIM-3 positivity was predominantly seen in clear cell (61.9%) and papillary (62.5%) renal cell carcinomas (RCCs) but - less commonly - also in Hodgkin’s (25.0%) and non-Hodgkin’s lymphomas (up to 9.1%), epithelial thymomas (6.9%), ovarian carcinomas (0.7%-1.4%), seminomas (0.4%), and several mesenchymal neoplasms (up to 16.0%). High TIM-3 expression of tumor cells was linked to low grade (p=0.0079), low UICC stage (p=0.0085), low pT (p<0.0001), and pN0 (p=0.0067) in clear cell RCC (ccRCC), and to pM0 (p=0.0177) in papillary RCC (pRCC). TIM-3 expression of macrophages occurred in all tumor entities but its relationship with parameters of aggressive disease varied between entities. A high quantity of TIM-3 positive macrophages was linked to unfavorable tumor parameters such as high grade (p<0.0001), advanced pT stage (p=0.0126), and distant metastasis (p=0.0069) in ccRCC, as well as high grade (p<0.0001), HER2 positivity (p=0.0015), and absence of estrogen (p<0.0001) and progesterone receptor (p=0.0187) expression in invasive breast carcinomas of no special type. A high number of TIM-3 positive macrophages was linked to favorable tumor parameters such as L0 (p=0.0333) and V0 (p=0.0161) in mismatch repair protein proficient colorectal carcinoma, low pT (p=0.0128), L0 (p=0.0333), and V0 (p=0.0161), as well as a lack of rete testis (p=0.0053) and spermatic cord infiltration (p=0.0365) in testicular seminoma. It is concluded that tumor cell TIM-3 expression among epithelial or mesenchymal tumors is largely restricted to RCCs where high expression is associated with parameters of non-aggressive disease. TIM-3 expression in tumor associated macrophages is abundant and its clinical significance varies between tumor entities. Citation Format: Maximilian Lennartz, David Dum, Christian Bernreuther, Patrick Lebok, Guido Sauter, Andreas H Marx, Ronald Simon, Christoph Fraune, Natalia Gorbokon, Eike Burandt, Sarah Minner, Stefan Steurer, Till S Clauditz, Till Krech. TIM-3 expression in human cancer: A tissue microarray study on 17, 172 patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3207.