Ex vivo host response to gastrointestinal cancer cells presented by autologous dendritic cells

Citation
A. Galetto et al., Ex vivo host response to gastrointestinal cancer cells presented by autologous dendritic cells, J SURG RES, 100(1), 2001, pp. 32-38
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Surgery,"Medical Research Diagnosis & Treatment
Journal title
JOURNAL OF SURGICAL RESEARCH
ISSN journal
0022-4804 → ACNP
Volume
100
Issue
1
Year of publication
2001
Pages
32 - 38
Database
ISI
SICI code
0022-4804(200109)100:1<32:EVHRTG>2.0.ZU;2-V
Abstract
Background. Dendritic cells (DCs) capture apoptotic tumors and cross-presen t their antigens in the MHC class I and class II pathways for recognition b y CD4+ and CD8+ T lymphocytes. Here we have tested the ability of fresh sur gically resected colon and gastric cancer tumors to specifically activate h ost T lymphocytes when presented by autologous DCs. Methods. DCs derived from adherent blood mononuclear cells of five patients , after a 7-day culture with GM-CSF and IL-4, were exposed to apoptotic aut ologous tumor (AAT) or apoptotic autologous peritumor normal (AAN) cells an d cultured 24 h with monocyte-conditioned medium to achieve full DC maturat ion. Tumor-specific response was evaluated as single-cell cytokine release in an enzyme-linked immunospot (ELISPOT) and as cytotoxicity in a cold targ et inhibition Cr-51-release assay. Results. AAT-DCs induced specific IFN-gamma by T lymphocytes of two patient s (rectal and gastric cancer), whereas in another two patients (rectal and gastric cancer) this response was depressed with a similar tumor-specific p attern and in one patient (rectal cancer) there was no response. Activation of IFN-gamma release was accompanied by tumor cytotoxicity and both respon ses were enhanced by IL-12, indicating the functional integrity of patients ' lymphocytes. Conclusion. These data show that T-cell memory against rectal/gastric carci noma antigens can be triggered by tumor-loaded autologous DCs. However, esc ape mechanisms may exist among tumors of the same histological origin that can inhibit this host response. A DC-based antitumor immunological monitori ng assay with autologous tumor biopsies may allow patients to be screened t o determine those who are suitable candidates for immune-based immunotherap y. (C) 2001 Academic Press.