The Potential of T Cell Immunoglobulin and Mucin-Domain Containing-3 (Tim-3) in Designing Novel Immunotherapy for Bladder Cancer

Abstract

: Targeting inhibitory receptors on T cells in the tumor sites can promote effective anti-tumor immunity in bladder cancer. Unfortunately, the main dilemma is that a large number of patients remain refractory to CTLA-4, PD-1, and PD-L1 blockade therapies. T-cell immunoglobulin and mucin domain 3 (Tim-3) is an inhibitory receptor expressed on T cells and innate immune cells. Both in vivo and in vitro data from patients with advanced cancers support the role of Tim-3 inhibition in satisfactory anti-tumor immunity. In bladder cancer, the expression level of Tim-3 significantly increases with advanced pathological grade and T stage. Therefore, rationality implies that designing novel monoclonal antibodies reactive with Tim-3 alone or in combination with other checkpoint inhibitors may indicate a favorable response in bladder cancer. Here, we aimed to investigate the possibility of targeting Tim-3 as a novel anti-cancer treatment for bladder cancer.

Increased Tim-3 and Gal-9 expression are related to poor prognosis in Oral Squamous Cell Carcinoma

“…Mohsenzadegan et all demonstrated that increased Tim3 expression causes tumor progression in bladder cancer. He also suggested that Tim3 can be a therapeutic target either alone or in combination with other checkpoint inhibitors (34) Similar to this Jia et al also observed poor prognosis with increased Tim3 expressions in non-small cell lung carcinoma (35). In the current study higher expressions of Gal9 were found in patients with advanced tumor stages.…”

T cell immunoglobulin and mucin domain-containing protein 3 is highly expressed in patients with acute decompensated heart failure and predicts mid-term prognosis

“…It has been previously reported that Tim-3 often acts as a negative regulator to mediate T cell exhaustion (27). The results of studies published so far mostly support the conclusion that Tim-3 inhibits T cell responses, especially when chronic stimuli are involved (28)(29)(30). In contrast, several reports provided evidence that Tim-3 could promote both T-lymphocyte proliferation and proinflammatory cytokine production under acute stimulation (14)(15)(16).…”

Immune Checkpoint Inhibitors in Cancer Therapy

“…Several antibodies and small compounds targeting various immune checkpoint proteins are in clinical development including B7H3, CD39, CD73, the adenosine A2A receptor, and CD47 [18]. Recent studies have identified several new immune checkpoint targets, such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT), V-domain Ig suppressor of T cell activation (VISTA), and so on [29]. These experiments indicated that the blockade of a single immune checkpoint may lead to compensatory upregulation of other checkpoint receptors in TME [30].…”