Open AccessVisualizing CTL/melanoma cell interactions: multiple hits must be delivered for tumour cell annihilation
Author(s) -
Caramalho Íris,
Faroudi Mustapha,
Padovan Elisabetta,
Müller Sabina,
Valitutti Salvatore
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00586.x
Subject(s) - ctl* , melanoma , cytotoxicity , cytotoxic t cell , context (archaeology) , cell , biology , lytic cycle , microbiology and biotechnology , cancer research , immunology , in vitro , genetics , paleontology , virus
It is well established that cytotoxic T lymphocytes (CTL) can kill target cells offering a very small number of specific peptide/MHC complexes (pMHC). It is also known that lethal hit delivery is a very rapid response that occurs within a few minutes after cell–cell contact. Whether cytotoxicity is efficient and rapid in the context of CTL interaction with target cells derived from solid tumours is still elusive. We addressed this question by visualizing the dynamics of human CTL interaction with melanoma cells and their efficiency in eliciting cytotoxicity. Our results show that in spite of CTL activation to lethal hit delivery, killing of melanoma cells is not efficient. Time‐lapse microscopy experiments demonstrate that individual CTL rapidly polarize their lytic machinery towards target cells, yet the apoptotic process in melanoma cells is defective or ‘delayed’ as compared to conventional targets. These results indicate that although CTL activation to lethal hit delivery can be viewed as a ‘digital’ phenomenon rapidly triggered by a few ligands, melanoma cell annihilation is an ‘analogue’ response requiring multiple hits and prolonged contact time.