Synthetic CD4+ T cell-targeted antigen-presenting cells elicit protective antitumor responses.
AuthorsCaserta S, Alessi P, Guarnerio J, Basso V, Mondino A,
JournalCancer Res
PubMed ID18413771
CD4(+) helper T cells are critical for protective immune responses and yet suboptimally primed in response to tumors. Cell-based vaccination strategies are under evaluation in clinical trials but limited by the need to derive antigen-presenting cells (APC) from patients or compatible healthy donors. To overcome these limitations, we developed CD4(+) ... More
Stored Fas ligand, a mediator of rapid CTL-mediated killing, has a lower threshold for response than degranulation or newly synthesized Fas ligand.
AuthorsHe JS, Gong DE, Ostergaard HL,
JournalJ Immunol
PubMed ID19949069
'CTL lyse target cells through the release of cytolytic granule mediators and expression of the death receptor ligand Fas ligand (FasL). We previously demonstrated that FasL is stored in vesicles distinct from cytolytic granules and is translocated to the cell surface within 15 min of TCR stimulation, followed by a ... More
Antigen-experienced CD4(+) T cells limit naïve T-cell priming in response to therapeutic vaccination in vivo.
AuthorsSchiering C, Guarnerio J, Basso V, Muzio L, Mondino A,
JournalCancer Res
PubMed ID20631073
'CD4(+) T cells play a central role in protective immunity. In a mouse tumor model, we previously found that tumor growth elicits natural CD4(+) T-cell responses, but impedes therapeutic vaccination. We show here that inhibition of vaccine-mediated naïve T-cell priming is due to the presence of a minor but distinct ... More
Chromogranin A regulates tumor self-seeding and dissemination.
AuthorsDondossola E, Crippa L, Colombo B, Ferrero E, Corti A,
JournalCancer Res
PubMed ID22139379
Cancer progression involves the seeding of malignant cells in circulation and the colonization of distant organs. However, circulating neoplastic cells can also reinfiltrate the tumor of origin. This process, called ... More
Ezrin and moesin function together to promote T cell activation.
The highly homologous proteins ezrin, radixin, and moesin link proteins to the actin cytoskeleton. The two family members expressed in T cells, ezrin and moesin, are implicated in promoting T cell activation and polarity. To elucidate the contributions of ezrin and moesin, we conducted a systematic analysis of their function ... More
Tyrosine phosphorylation of a 100-kDa protein is correlated with cytotoxic T-lymphocyte function. Evidence from cis unsaturated fatty acid and phenylarsineoxide inhibition.
AuthorsAnel A, Kleinfeld AM
JournalJ Biol Chem
PubMed ID8394347
Cis unsaturated but not saturated fatty acids (FA) have been shown to specifically inhibit certain early responses in cytotoxic T-lymphocytes (CTL) including the rise in intracellular calcium, degranulation, and lethal hit delivery. They do not, however, affect other early events such as the turnover of phosphatidylinositol, T-cell receptor recognition, and ... More
A tyrosine phosphorylation requirement for cytotoxic T lymphocyte degranulation.
AuthorsAnel A, Richieri GV, Kleinfeld AM
JournalJ Biol Chem
PubMed ID7511589
Phorbol myristate acetate (PMA) plus ionomycin induces the tyrosine phosphorylation of several cytotoxic T lymphocyte (CTL) substrates, including one with an apparent molecular weight of 100,000 (pp100) in cloned murine CTL. cis-Unsaturated fatty acids and low concentrations of phenylarsine oxide specifically inhibit the tyrosine phosphorylation of pp100. Genistein also inhibits ... More