Sialic acid blockade boosts tumor immunity

22 May 2018

Christian Büll (photo), Natasja Balneger and Gosse Adema from the Radiotherapy and OncoImmunology Laboratory (ROI) of the Department of Radiation Oncology, theme Cancer development and immune defense, found that sialic acid sugars on the surface of cancer cells modulate the tumor microenvironment and limit the anti-tumor immunity. Blocking the expression of sialic acids in tumors with a sialic acid mimetic enhanced anti-tumor immunity alone or in combination with existing immunotherapies. This collaborative work together with the groups of Thomas Boltje (Molecular Chemistry) and Johan van der Vlag (Nephrology) was recently published in Cancer Research.

Publication: Link.

Christian Bull
Natasja Balneger
Gosse Adema

Cancer cells cover their surface with a dense layer of sialic acid sugars that contribute to multiple aspects of the disease. Sialic acids support cancer cell development, migration and metastasis and several studies suggest that these sugars contribute to the formation of an immunosuppressive tumor microenvironment which limits the immune system's natural capacity to detect and eradicate cancer cells. In this recent work, the team of Gosse Adema and coworkers used a sialic acid mimetic to block sialic acid expression in mouse tumor models. They found that sialic acid blockade with this compound was especially effective in tumor cells leading to a strong reduction in tumor growth. Strikingly, treatment with the sialic acid mimetic increased the number of effector CD8+ T cells in the tumor microenvironment while reducing the number of immunosuppressive cells. Further mechanistic studies showed that sialic acid blockade facilitated the interaction between effector CD8+ T cells and tumor cells leading to enhanced tumor destruction. Sialic acid blockade treatment synergized with CD8+ T cell transfer and other forms of immunotherapy directed at inducing anti-tumor immune responses. Altogether, this study emphasizes the crucial role of sialic acids in tumor immune evasion and provides proof of concept that sialic acid blockade creates a tumor microenvironment permissive for CD8+ T cell-mediated tumor immunity.