| Summary: | The quantity of T-lymphocytes reaching the draining lymph nodes from tumors is likely
important to mount effective distant responses and for the establishment of long term
systemic memory. Looking into mechanisms behind lymphocyte egress, we directed
our attention to leukocyte adhesion mechanisms inside tumors. Here we demonstrate
that activated T-cells form intra-tumor aggregates in a LFA-1-ICAM-1-dependent fashion
in mouse models of melanoma and breast cancer. We also provide evidence of the
presence of T-cell clusters in primary human melanoma. Disruption of LFA-1-ICAM-1
interactions, and thereby T-cell clustering, enhances the arrival of activated CD8+
T-cells to tumor draining lymph nodes in both transplanted and spontaneous cancer
models. Interestingly, upon ICAM-1 blockade, the expression of the chemotactic
receptor CCR7 augments in tumor infiltrating lymphocytes and in in-vitro de-clustered
T cells, as well as their ability to transmigrate across lymphatic endothelial cells. We
propose that ICAM-1-mediated homotypic T-lymphocyte aggregation may serve as a
tumor-mediated immune retention mechanism entrapping activated CD8+ T cells in
the tumor microenvironment. Modulation of T-cell adhesion may be of use to improve
the transit of activated lymphocytes toward the lymph nodes and their subsequent
recirculation.
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