Behavior of immune players in the tumor microenvironment

Tumors recruit various immune cells with seemingly contrasting functions. Yet, the precise role of these cells in situ remains vastly unknown. This review presents a new discovery effort that employs intravital imaging to study immune players directly in tissues.

Cytotoxic T lymphocytes (CTLs) that recognize cognate antigenic peptide can infiltrate tumors from the periphery to the center, and physically engage and eliminate antigen-presenting tumor cells. Nevertheless, the reported kinetics for tumor cell killing by CTLs in vivo is surprisingly low as it takes several hours for one CTL to eliminate one tumor cell. Also, T regulatory (Treg) cells can create a suppressive milieu that restricts the release of CTL cytotoxic granules, which protects tumor cells from being killed. CTLs may be further subverted during lengthy interactions with tumor-associated macrophages (TAMs). Finally, TAMs can directly facilitate tumor invasion by recruiting tumor cells nearby vessels and promoting their intravasation.

Intravital imaging has started to uncover tumor-related immune events as they unfold in vivo. The technology should be exploited in the coming years to dissect further the tumor microenvironment and to define therapeutics that augment antitumor immunity.