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Anti‐L‐selectin monoclonal antibody treatment in mice enhances tumor growth by preventing CTL sensitization in peripheral lymph nodes draining the tumor area
Author(s) -
Rosato Antonio,
Zambon Annalisa,
Macino Beatrice,
Mandruzzato Susanna,
Bronte Vincenzo,
Milan Gabriella,
Zanovello Paola,
Collavo Dino
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960315)65:6<847::aid-ijc23>3.0.co;2-#
Subject(s) - ctl* , spleen , monoclonal antibody , lymph , immunology , cytotoxic t cell , high endothelial venules , immune system , medicine , immunotherapy , l selectin , antibody , biology , pathology , cd8 , cell adhesion molecule , in vitro , biochemistry
To examine the in vivo contribution of L‐selectin in the sensitization of tumor‐specific CTL, we investigated the effects of treatment with the anti‐L‐selectin monoclonal antibody (MAb) MEL‐14 on the immune response to Moloney‐murine sarcoma virus (M‐MSV)‐induced tumors, which exhibit spontaneous regression following generation of a strong virus‐specific CTL response. Daily systemic administration of MEL‐14 for 10 days to M‐MSV‐injected mice gave rise to larger sarcomas that persisted for a longer time, compared with those arising in control mice injected with virus only. The enhanced tumor growth could not be attributed to cytotoxic activity on leukocytes by MEL‐14 since no reduction in the total cell number was detected in peripheral blood and spleen of MAb‐treated mice. Evaluation of the immunological response in MAb‐treated animals revealed a strong reduction in the generation of virus‐specific CTL precursors (CTLp) in tumor‐draining peripheral lymph nodes (PLN) 10 and 15 days after M‐MSV injection, while in spleen, where lymphocyte localization is independent of L‐selectin expression, CTLp generation was only delayed. By day 20, when tumors had begun to regress, the CTLp number showed a marked increase in both spleen and local PLN, where naive recirculating CTL could now enter because L‐selectin was no longer down‐regulated or blocked by the injected MAb. Our findings indicate that functional inactivation of L‐selectin by MEL‐14 treatment prevented migration of naive L‐selectin + CTL through high endothelial venules (HEV) and their accumulation in PLN draining the tumor area, thereby precluding the initiation of a tumor‐specific CTL response that takes place primarily at this site. © 1996 Wiley‐Liss, Inc.