Emerging evidence underscores a key role for the tumor microenvironment in supporting or suppressing cancer immunity. Of note, pro- and antitumor immune activity is controlled by not only the types of immune cells present but also their spatial arrangement within a tumor. This evidence is supported by the observation that the organization of immune cells in specialized immune niches is more predictive for clinical outcome and immunotherapy response than is the mere presence of tumor immune infiltrates. In this review, we explore how spatial compartmentalization modulates immune function through concerted cellular interactions, localized signaling cascades, and the generation of protective environments. We integrate current knowledge on both established and emerging immune niches with variable complexity-shaped by cell diversity, cell density, and structural organization-and their functional impact on cancer immunity. Finally, we discuss the compelling therapeutic opportunities offered by the induction or modulation of these niches in tumors.
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