Emerging Immune Checkpoints - ILDR2

ILDR2, short for Immunoglobulin-Like Domain-Containing Receptor 2, has emerged as a promising immune checkpoint in the quest to enhance cancer immunotherapy. With its unique structural features and intricate regulatory functions, ILDR2 has captivated the attention of scientists and researchers.

By gaining a deeper understanding of ILDR2 and its implications in the immune landscape, Creative Biolabs can help researchers potentially unravel novel avenues for therapeutic interventions in cancer treatment.

Introduction to ILDR2

ILDR2 belongs to the immunoglobulin superfamily, a diverse group of cell surface and secreted proteins involved in immune responses and cell-cell interactions. This superfamily encompasses a wide array of receptors and ligands that influence immune cell behavior, including T cells, B cells, and antigen-presenting cells.

ILDR2 is expressed in various immune cell subsets, including T cells and natural killer (NK) cells, where it exerts intricate control over immune activation and tolerance. By engaging with its ligands or interacting with other immune checkpoints, ILDR2 can exert regulatory effects that shape the delicate balance between immune surveillance and immune tolerance.

Predicted structure of major ILDR2 isoforms.Fig 1. Predicted structure of major ILDR2 isoforms. (Watanabe, 2013)

Functional Significance of ILDR2

Research suggests that ILDR2 engagement can lead to diverse outcomes, ranging from immune activation to immune suppression, depending on the cellular context and signaling pathways involved. This intriguing duality makes ILDR2 a compelling target for therapeutic manipulation.

  • One aspect that sets ILDR2 apart from other immune checkpoints is its interaction with unique ligands. ILDR2 has been found to interact with immune-related proteins such as HVEM, BTLA, and CD160, among others. These interactions can modulate immune cell functions.
  • Preclinical studies have demonstrated that dysregulated ILDR2 expression or activity can have profound effects on tumor growth, metastasis, and immune evasion. This suggests that targeting ILDR2 could provide a new strategy for unleashing the immune system's full potential against cancer.

ILDR2 as A Therapeutic Target

Given its emerging role as an immune checkpoint, ILDR2 represents a tantalizing target for the development of novel immunotherapies. Building upon the success of immune checkpoint inhibitors, researchers are actively exploring strategies to modulate ILDR2 function and enhance anti-tumor immune responses.

Several therapeutic approaches are being investigated to target ILDR2, including

  • Monoclonal antibodies
  • Engineered T-cell receptors (TCRs)
  • Chimeric antigen receptor (CAR) T-cell therapies
  • Combination therapies

By leveraging these strategies, researchers aim to restore immune surveillance and bolster immune cell responses against cancer cells. The goal is to unleash the full potential of ILDR2 as a therapeutic avenue.

Diagnostic and Prognostic Potential of ILDR2

ILDR2 also holds promise as a diagnostic and prognostic biomarker in cancer. Emerging evidence suggests that aberrant ILDR2 expression is associated with specific tumor types and can serve as a valuable indicator of disease progression and prognosis.

  • By evaluating ILDR2 expression levels in samples, clinicians can potentially gain insights into disease aggressiveness and tailor treatment strategies accordingly.
  • Studies have revealed correlations between high ILDR2 expression and favorable treatment outcomes, suggesting that ILDR2 could serve as a predictive biomarker for therapeutic response.

ILDR2, an intriguing member of the immune checkpoint landscape, holds immense promise as a target for therapeutic intervention. Its unique structural features, diverse ligand interactions, and involvement in immune regulation make ILDR2 an exciting area of research.


  1. Chapoval A I, et al. Immune checkpoints of the B7 family. Part 2. Representatives of the B7 family B7-H3, B7-H4, B7-H5, B7-H6, B7-H7, and ILDR2 and their receptors. Russian Journal of Bioorganic Chemistry, 2019, 45: 321-334.
  2. Bolandi N, et al. The positive and negative immunoregulatory role of B7 family: promising novel targets in gastric cancer treatment. International Journal of Molecular Sciences, 2021, 22(19): 10719.
  3. Watanabe K, et al. ILDR2: an endoplasmic reticulum resident molecule mediating hepatic lipid homeostasis. PLoS One. 2013, e67234.

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