Ex vivo host response to gastrointestinal cancer cells presented by autologous dendritic cells.
BACKGROUND
Dendritic cells (DCs) capture apoptotic tumors and cross-present their antigens in the MHC class I and class II pathways for recognition by CD4+ and CD8+ T lymphocytes. Here we have tested the ability of fresh surgically resected colon and gastric cancer tumors to specifically activate host 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 autologous tumor (AAT) or apoptotic autologous peritumor normal (AAN) cells and cultured 24 h with monocyte-conditioned medium to achieve full DC maturation. Tumor-specific response was evaluated as single-cell cytokine release in an enzyme-linked immunospot (ELISPOT) and as cytotoxicity in a cold target inhibition (51)Cr-release assay.


RESULTS
AAT-DCs induced specific IFN-gamma by T lymphocytes of two patients (rectal and gastric cancer), whereas in another two patients (rectal and gastric cancer) this response was depressed with a similar tumor-specific pattern and in one patient (rectal cancer) there was no response. Activation of IFN-gamma release was accompanied by tumor cytotoxicity and both responses were enhanced by IL-12, indicating the functional integrity of patients' lymphocytes.


CONCLUSIONS
These data show that T-cell memory against rectal/gastric carcinoma antigens can be triggered by tumor-loaded autologous DCs. However, escape mechanisms may exist among tumors of the same histological origin that can inhibit this host response. A DC-based antitumor immunological monitoring assay with autologous tumor biopsies may allow patients to be screened to determine those who are suitable candidates for immune-based immunotherapy.
Galetto
A
A
Department of Oncology, Unity of Oncological Surgery, Azienda Ospedaliera San Giovanni, Turin, Italy.
Contarini
M
M
Sapino
A
A
Cassoni
P
P
Consalvo
E
E
Forno
S
S
Pezzi
C
C
Barnaba
V
V
Mussa
A
A
Matera
L
L
D000230:Adenocarcinoma; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D018279:Carcinoma, Signet Ring Cell; D015179:Colorectal Neoplasms; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D013274:Stomach Neoplasms; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000276:immunology
D000951:Antigens, Neoplasm; D018664:Interleukin-12; D007371:Interferon-gamma