Live
imaging technology is becoming
an increasing popular tool to visualize real-time cellular events in the tumor
microenvironment during metastatic progression. In the AACR 2012 symposium
entitled, “Immune Cell Function and Cancer In Vivo: Visualizing Friends
and Foes”, there were two remarkable presentations showing stunning
real-time revelations on the role of immune cells in
cancer. 

First, Dr. John Condeelis used multiphoton microscopy in a
mammary imaging window to monitor macrophage and tumor cell interactions in a
metastatic mouse PYMT breast cancer model. His videos revealed a stunning array
of “streaming chemotaxis” in which macrophages and cancer cells are
alternatively lined up in a stream during their trafficking to the nearby blood
vessels. Condeelis further revealed clusters of macrophages along the blood
vessels that are colocalized with the site to tumor cell intravasation,
suggesting the integral role of macrophages in the cancer cell’s journey into
circulation. This concept was supported by similar in vivo monitoring of PYMT
mice defective in CSF production (macrophage-deficient), revealing that the
absence of macrophages resulted in a significant reduction in streaming
chemotaxis and intravasation.  Condeelis further concluded his talk with
the potential molecular mechanism underlying the effects of macrophages on
metastasis.

Departing from Condeelis’ theme is the talk by Dr. Christopher Contag, who
used real-time whole-body tracing to track the synergistic tumor-killing
activity of cytokine-induced killer (CIK) cells and oncolytic vaccinia virus
(vv) in a mouse xenograft model of ovarian cancer. CIK cells can kill tumor
cells specifically by targeting the cancer-specific marker NKG2D (stress
associated antigen). Using a combination of bioluminescent imaging (for
vaccinia virus expressing luciferase reporter) and far red cy5.5 fluorescence
imaging (for cy5.5 conjugated CIK cells), Contag discovered that CIK cells
serve as an effective delivery vessel for vaccinia virus- enhancing  the
delivery of vaccinia virus specifically to the tumor site. Importantly, CIKs
must be pre-infected with vaccinia virus, and that vaccinia virus must be
delivered by CIKs, in order to achieve this level tumor specificity, suggesting
remarkable synergy between CIKs and vaccinia virus. 

These breathtaking studies are the few examples showing how powerful in vivo
imaging technologies have revolutionized cancer research. Gone are the old school methods
that produce “still” evidence of cancer progression. These new technologies
allow scientists to perceive the cellular events governing cancer metastasis,
or to trace the effectiveness of new anti-cancer treatments; all with real-time
and single-cell clarity.

Details about technologies
highlighted in the AACR in vivo imaging seminar can be found below

1) Dr. Contag’s newest implantable confocal microscope featuring 3D YZ and XY
stacked tumor videos, as well as Pulse Electron Avalanche Knife tissue sampler
to allow concise and accurate tissue sampling. Dr. Contag is the Director of
the Stanford Center for Photomedicine: http://med.stanford.edu/profiles/mips/researcher/Christopher_Contag/ 

2) Evrogen’s far red fluorescent reporters demonstrating low long-term
cytotoxicity, and is ideal for tracing cancer cell metastasis and their
susceptibility to treatments. More information about this technology can be
found at http://www.nature.com/nmeth/journal/v6/n5/pdf/nmeth.f.249.pdf