Biomedical Engineering Reference
In-Depth Information
unable to ei ciently enter the tumor tissue and kill tumor cells (Appay
et al.
2006).
Endothelial cells in various tumors express lower levels of adhesion molecules
essential in leukocyte recruitment, including ICAM-1, VCAM-1, and E-selectin
(Dirkx
et al.
2003, Weishaupt
et al.
2007, Clark
et al.
2008). Tumor endothelial cells
are also unresponsive to inl ammatory cytokines that induce adhesion molecule
expression (Grii oen 2008). Interestingly, treatment of squamous cell carcinomas
with a topical TLR agonist can enhance expression of E-selectin on tumor vessels,
resulting in recruitment of CLA+ CD8 T cells and tumor regression (Clark
et al.
2008). Excessive angiogenesis will also result in abnormal tumor vessel architecture
that can block recruitment of T cells and even drug delivery to the tumor (Manzur
et al.
2008). Combining immunotherapy with angiostatic and proinl ammatory
agents has led to better prognoses in solid tumor therapy (Cirone
et al.
2004, Ganss
et al.
2004). h ese i ndings have important implications for the design of future
immunotherapy protocols, which will depend on the identii cation of methods to
upregulate the expression of homing molecules on tumor vasculature or otherwise
bypass this block to ef ective T cell function.
SUMMARY
• Leukocyte homing is a crucial element of immune surveillance and
immune response, playing an important role in both health and disease.
• Leukocyte homing depends on a stepwise process of tethering, rolling,
activation, i rm adhesion and transmigration.
• Every step in the homing cascade is necessary, but individually insui cient,
to direct leukocyte recruitment and retention, thus providing a mechanism
for specii city and selectivity.
• Keratinocytes are important and ot en under-appreciated participants in
cutaneous immunity.
• Immune memory encompasses not only specii city for antigen, but also a
homing bias to the anatomical site of i rst exposure.
• h erapeutic strategies targeting key molecules in the recruitment paradigm
have led to ef ective treatments for skin inl ammation and malignancies.
Abbreviations
APC
antigen presenting cells
CCR
CC chemokine receptor
CCL
CC chemokine ligand
CD
cluster of dif erentiation
dDC
dermal dendritic cells
ERK
extracellular signal-regulated kinase
