This model served as a preliminary screening tool to identify immune cell responses to VSV- NDV therapy

The gap

Evidence profile

Sourced from the future work and inline gaps of the source papers, classified as general, drawn from work published between 2024 and 2026, spanning 4 journals. Those papers have been cited 8 times in total.

Supporting evidence — 4 representative gaps

• Regulatory T cells in the bladder cancer tumor microenvironment: mechanisms of immune suppression and therapeutic opportunities (2026) · Frontiers in Molecular Biosciences · doi

  Considering their immunosuppressive roles in the BC TME, Tregs represent potential therapeutic targets. However, their systemic depletion can compromise immune tolerance and lead to immune-related toxicities. Therefore, therapeutic strategies should aim to selectively modulate tumor-infiltrating Tregs directly involved in local immune suppression rather than broadly eliminating Tregs in peripheral tissues (Tay et al., 2023). Among potential targets, CCR8 is a promising marker of highly suppressive tumor-infiltrating Tregs. From a therapeutic perspective, CCR8 is appealing as it may facilitate relatively selective targeting of intratumoral Tregs while preserving peripheral Tregs, which are crucial for systemic immune tolerance. Preclinical and translational evidence suggests that CCR8 blockade destabilizes intratumoral Tregs and enhances antitumor immunity in MIBC (Wang et al., 2020), suggesting that CCR8-positive Tregs contribute immunosuppressive niche. Experimental to maintaining an studies in other tumor models have also shown that selective depletion of CCR8-positive tumor-infiltrating Tregs enhances CD8-positive T cell responses and synergizes with PD-1 blockade (Van Damme et al., 2021; Kidani et al., 2022). Additional checkpoint molecules expressed by tumor-infiltrating Tregs, including cytotoxic T-lymphocyte-associated protein 4, PD-1, T cell immunoreceptor with Ig and ITIM domains, and possibly lymphocyte activation gene-3, may also contribute to immunosuppressive signaling; however, their relevance as selective Treg-directed targets in BC remains investigational (Tay et al., 2023). CCR4 may also be a relevant chemokine receptor involved in Treg recruitment in BC. The C-C motif chemokine ligand 17–CCR4 axis promotes Treg accumulation, whereas CCR4 blockade reduces Treg infiltration and prolongs survival in a canine spontaneous BC model. CCR4- positive Tregs have also been observed in human BC tissues, suggesting that this pathway warrants further investigation (Maeda et al., 2019). However, CCR4 is not specific to tumor- infiltrating Tregs and may also be expressed by other T cell subsets. Therefore, CCR4-directed approaches should be considered as potential strategies to modulate Treg recruitment and trafficking rather than as established selective Treg-targeted therapies for human BC. Overall, selective Treg targeting should be viewed as a strategy for remodeling the bladder TME rather than merely depleting Tregs (Figure 2B). Such approaches may be particularly beneficial when combined with therapies that activate antitumor immunity, including BCG and immune checkpoint blockade therapies. Although not designed as a Treg-targeted therapy, a recent phase 3 trial combining BCG therapy with PD-L1 blockade supports the broader concept that modulation of the immunosuppressive bladder TME enhances existing immunotherapeutic strategies (De Santis et al., 2025).

  generalfuture work
  Keywords: tregs treg tumor immune infiltrating selective blockade immunosuppressive positive potential therapeutic targets strategies rather enhances
• The PVR-TIGIT/CD96/CD226 axis: a novel immune checkpoint target in ovarian cancer (2026) · Frontiers in Immunology · doi

  CD155 has emerged as a critical immune checkpoint in ovarian cancer, functioning at the crossroads of immune regulation and tumor progression. By interacting with TIGIT and CD96 while competing with CD226, CD155 orchestrates a complex signaling network that drives T cell exhaustion, NK cell dysfunction, and regulatory T cell expansion, ultimately promoting immune evasion. Its expression on tumor cells, dendritic cells, and macrophages, as well as the presence of soluble isoforms, further contributes to the establishment of an immunosuppressive tumor microenvironment. Therapeutic strategies aimed at disrupting the CD155 axis— whether by blocking inhibitory interactions or restoring CD226- mediated co-stimulation—are under active investigation. Monoclonal antibodies, bispecific constructs, and engineered CAR-T or NK cell therapies have demonstrated encouraging preclinical results and early-phase clinical potential. However, several challenges must be addressed before these approaches can be widely translated into clinical practice. First, the dual role of CD155 as both an inhibitory and activating ligand complicates the design of targeted interventions. Non-selective blockade may unintentionally suppress beneficial CD226 signaling. Second, the regulation of CD155 expression is

  generalfuture work
  Keywords: cell immune tumor regulation signaling expression cells inhibitory clinical emerged critical checkpoint ovarian cancer functioning
• CAIT cells and TRA clonotypes: emerging immunological candidates for IBD therapy (2026) · Journal of Translational Genetics and Genomics · doi

  The work by this study significantly broadens our understanding of T-cell immunity in IBD. Through systematic TRA repertoire profiling across multiple cohorts and disease stages, the study identifies CAIT-cell expansion as a persistent and clinically relevant immune signature of CD. It also provides a valuable repertoire-level resource of disease-associated TRA clonotypes for future mechanistic and translational studies. CAIT cells represent a rational candidate target for antibody-mediated blockade, selective cellular depletion, or other immune-modulating strategies in refractory CD. However, before CAIT-directed therapies can be translated into clinical practice, further studies are needed to define the antigen specificity, tissue distribution, functional phenotype, and pathogenic contribution of CAIT cells. Future research should integrate high-throughput antigen discovery, single-cell transcriptomics, paired TCR sequencing, and matched intestinal mucosal sampling. Such approaches will help distinguish causal immune drivers from inflammation-associated bystanders. Page 484 Zhang et al. J Transl Genet Genom. 2026;10:481-5 Overall, this study illustrates the power of multi-cohort, unbiased TCR repertoire analysis in uncovering hidden immune drivers of complex inflammatory diseases. As immunotherapy continues to evolve, precision targeting of pathogenic immune cell populations may become an increasingly important strategy for improving outcomes in patients with IBD. DECLARATIONS Authors’ contributions Wrote the manuscript and has directly accessed and verified the underlying data reported in the manuscript:

  generalfuture work
  Keywords: immune cell cait repertoire disease associated future cells antigen pathogenic drivers manuscript broadens understanding immunity
• A Novel Chimeric Oncolytic Virus Mediates a Multifaceted Cellular Immune Response in a Syngeneic B16 Melanoma Model (2024) · Cancers · cited 8× · doi

  This model served as a preliminary screening tool to identify immune cell responses to VSV- NDV therapy, which will certainly need to be validated in more immunologically predictive models and compared across distinct tumor indications. While it was beyond the scope of this work to characterize the precise mechanism and cross-talk among the individual immune cell types, a critical dependence on the cytotoxic T cell response for the therapeutic outcome of VSV-NDV therapy is strongly implicated by the complete ablation of tumor responses in the context of CD8+ T cell depletion.

  generalinline gaps
  Keywords: cell immune responses therapy tumor model served preliminary screening tool identify certainly need validated immunologically

Questions about this gap