Intravital imaging of anti-tumor immune response and the tumor microenvironment

Abstract

Tumor growth, invasiveness, and metastasis are dynamic processes involving cancer interactions with the extracellular matrix, the vasculature, and various types of non-cancerous host cells that form the tumor stroma. An often-present stromal component is the immune cells, such as tumor-associated myeloid and lymphocytic infiltrates, yet endogenous anti-tumor immune responses are typically ineffective in tumor rejection and may even contribute to the progression of some cancers. How exactly cancer cells interact with the stroma and invade healthy tissues while avoiding anti-tumor immune responses, and which interactions should be targeted for anti-tumor therapy, can now be studied by minimally invasive observation using multi-photon and other low impact confocal microscopy techniques and fluorescent animal tumor models. Intravital video microscopy has already been instrumental in defining the roles and modes of cellular motility in the angiogenic process and during tissue invasion at the tumor margin. In the hands of cancer immunologists, intravital video microscopy is beginning to unravel the complexity of effector and suppressory lymphocytic interactions in tumors and in the draining lymphoid organs. As the intravital microscopy approach is beginning to move beyond fundamental description and into analyzing the molecular underpinnings of cell's dynamics, future technical advances will undoubtedly provide yet deeper insight while stitching together a systems dynamics view of cancer-host interactions that will keep on inspiring cancer researchers and therapists.

Two-Photon and Second Harmonic Microscopy in Clinical and Translational Cancer Research

“…4,19,54,63 Other colleagues have discussed application of intravital TPM to studies of stromal cell dynamics and interactions in the tumor microenvironment, 38,70 and to understanding the mechanisms and contributions of immune cells and the immune response to tumor pathology. 121 …”

Cytotoxic T Lymphocyte Antigen-4 Blockade Enhances Antitumor Immunity by Stimulating Melanoma-Specific T-cell Motility

“…16). Because checkpoint blockade is known to affect TIL composition and tumors have been shown to contain both tumor-specific and nonspecific T cells (13), the direct effects of a-CTLA-4 antibodies on tumor-specific immune responses have yet to be determined.…”

“…Initial studies of tumor-specific immune responses used transplantable tumors expressing the foreign antigen ovalbumin (OVA) and adoptively transferred OVA-specific OT-I CD8 þ T cells (reviewed in ref. 13)). More recent work defined the steadystate dynamics of melanoma-specific CD8 þ pmel-1 T cells, which recognize the self-antigen gp100 in the context of H2-D b (14), and compared them with OT-I T cells in the absence of OVA (15).…”

Visualization of Myelomonocytic Cells in Tumours

“…Jain and colleagues visualized tumor cell localization, angiogenesis, as well as leukocyte-blood vessel interactions and vessel permeability with high spatial and temporal resolution (Brown et al 2001). Since then this approach has been adopted by researchers in the field of tumor biology to study tumor cell migration and tissue invasion, as well as angiogenesis, matrix remodeling and metastasis (reviewed in (Zal and Chodaczek 2010)). …”