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Viewing Siglecs through the lens of tumor immunology

Isabella Fraschilla1, Shiv Pillai1

  • 1Ragon Institute of MGH, MIT and Harvard, Harvard Medical School, Cambridge, MA, USA.

Immunological Reviews
|March 5, 2017
PubMed

Insights

Sialic acid-binding immunoglobulin-like lectins (Siglecs) impact anti-tumor immunity. Inhibitory Siglecs like Siglec 9 and Siglec 7 can dampen immune responses, while CD169 may facilitate tumor cell recognition and clearance.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Sialic acid-binding immunoglobulin-like lectins (Siglecs) are key regulators of immune cell function.
  • Many Siglecs act as inhibitory receptors, potentially suppressing anti-tumor immune responses.
  • Siglec 9 on neutrophils and Siglec 7 on NK cells exemplify inhibitory Siglecs relevant to cancer immunity.

Purpose of the Study:

  • To explore the multifaceted roles of Siglecs in anti-tumor immunity.
  • To investigate the dual function of CD169 as an adhesion molecule and facilitator of tumor-derived material uptake.
  • To highlight the current understanding of Siglec involvement in cancer, primarily from animal models.

Main Methods:

  • Review and synthesis of existing literature on Siglec function in cancer.
  • Analysis of Siglec expression and function on innate and adaptive immune cells in tumor microenvironments.
  • Examination of CD169's proposed mechanisms in recognizing and internalizing tumor-associated sialic acids.

Main Results:

  • Inhibitory Siglecs (Siglec 9, Siglec 7) can attenuate immune cell activity against tumors.
  • CD169 may promote anti-tumor immunity by facilitating the recognition and clearance of tumor-derived apoptotic bodies and exosomes.
  • Siglec involvement in cancer is predominantly studied in preclinical animal models.

Conclusions:

  • Siglecs exhibit complex, context-dependent roles in anti-tumor immunity, acting as both suppressors and facilitators.
  • Targeting Siglec function represents a promising therapeutic avenue for cancer treatment.
  • Clinical investigation of Siglec modulators in cancer is anticipated in the near future.
Keywords:
Sigleccancer/tumor immunologyhypersialylationimmune evasionimmune regulationinhibitory receptorsialic acid

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