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The January 2012 special issue presents two important strategies for generating potent and lasting anti-tumor immunity. The first strategy is to subvert immune suppressive networks in the tumor microenvironment. The second strategy is to optimize conventional and anti-biological modalities to directly target tumor and adjacent tumor tissue, and mobilize and expand anti-tumor immunity in the tumor microenvironment which results in tumor eradication. Further background information on this important topic is available through the accompanying web focus which links to related articles from across Springer Nature.