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T-Cell Distribution and Adhesion Receptor Expression in Metastatic Melanoma
Ist Teil von
Clinical cancer research, 2007-05, Vol.13 (9), p.2549-2556
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2007
Quelle
MEDLINE
Beschreibungen/Notizen
Purpose: Metastatic malignant melanoma is a devastating disease with a poor prognosis. Recent therapeutic trials have focused on immunotherapy
to induce development of endogenous antitumor immune responses. To date, such protocols have shown success in activation of
tumor-specific CTL but no overall improvement in survival. To kill tumor, antigen-specific CTL must efficiently target and
enter tumor tissue. The purpose of this study was to examine the pathway of leukocyte migration to metastatic melanoma.
Experimental design: Peripheral blood and metastatic melanoma tissues ( n = 65) were evaluated for expression of adhesion molecules using immunohistochemistry of tumor sections and flow cytometry
of tumor-associated and peripheral blood CTL and compared with healthy controls. CTL expressing T-cell receptors for the melanoma
antigen MART-1 were identified in a subset of samples by reactivity with HLA-A2 tetramers loaded with MART-1 peptide.
Results: Results show that the majority of metastatic melanoma samples examined do not express the vascular adhesion receptors E-selectin
(CD62E), P-selectin (CD62P), and intercellular adhesion molecule-1 (CD54) on vessels within the tumor boundaries. Strong adhesion
receptor expression was noted on vessels within adjacent tissue. Tumor-associated T lymphocytes accumulate preferentially
in these adjacent areas and are not enriched for skin- or lymph node–homing receptor phenotype.
Conclusion: Expression of leukocyte homing receptors is dysregulated on the vasculature of metastatic melanoma. This results in a block
to recruitment of activated tumor-specific CTL to melanoma metastases and is a likely factor limiting the effectiveness of
current immunotherapy protocols.