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Intravital imaging of CD8+ T cell function in cancer

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Abstract

Recent technological advances in photonics are making intravital microscopy (IVM) an increasingly powerful approach for the mechanistic exploration of biological processes in the physiological context of complex native tissue environments. Direct, dynamic and multiparametric visualization of immune cell behavior in living animals at cellular and subcellular resolution has already proved its utility in auditing basic immunological concepts established through conventional approaches and has also generated new hypotheses that can conversely be complemented and refined by traditional experimental methods. The insight that outgrowing tumors must not necessarily have evaded recognition by the adaptive immune system, but can escape rejection by actively inducing a state of immunological tolerance calls for a detailed investigation of the cellular and molecular mechanisms by which the anti-cancer response is subverted. Along with molecular imaging techniques that provide dynamic information at the population level, IVM can be expected to make a critical contribution to this effort by allowing the observation of immune cell behavior in vivo at single cell-resolution. We review here how IVM-based investigation can help to clarify the role of cytotoxic T lymphocytes (CTL) in the immune response against cancer and identify the ways by which their function might be impaired through tolerogenic mechanisms.

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Abbreviations

ALV:

Antigenic loss variant(s)

APC:

Antigen presenting cell(s)

CTL:

Cytotoxic T lymphocyte(s)

DC:

Dendritic cell(s)

EGFP:

Enhanced green fluorescent protein

FRET:

Foerster resonance energy transfer

HEV:

High endothelial venule(s)

IVM:

Intravital microscopy

LN:

Lymph node(s)

MHC:

Major Histocompatibility Complex

MP-IVM:

Multiphoton intravital microscopy

MPM:

Multiphoton microscopy

MTOC:

Microtubule organizing center

SLO:

Secondary lymphoid organ(s)

SMAC:

Supramolecular activation cluster

TCR:

T cell receptor(s)

Treg:

Regulatory T cell(s)

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Acknowledgements

We would like to thank Drs. Mikael Pittet and Cathryn Nagler for helpful discussions and critical reading of the manuscript. T.R.M. is supported by NIH grant 4 R00 AI073457 - 02 and C.A.B. is supported by a grant from the Deutsche Forschungsgemeinschaft.

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  1. Center for Immunology and Inflammatory Diseases and Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA, 02129, USA

    Thorsten R. Mempel & Christian A. Bauer

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Mempel, T.R., Bauer, C.A. Intravital imaging of CD8+ T cell function in cancer. Clin Exp Metastasis 26, 311–327 (2009). https://doi.org/10.1007/s10585-008-9196-9

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