PMID- 11516202 OWN - NLM STAT- MEDLINE DCOM- 20010920 LR - 20181130 IS - 0022-4804 (Print) IS - 0022-4804 (Linking) VI - 100 IP - 1 DP - 2001 Sep TI - Ex vivo host response to gastrointestinal cancer cells presented by autologous dendritic cells. PG - 32-8 AB - 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. CONCLUSION: 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. CI - Copyright 2001 Academic Press. FAU - Galetto, A AU - Galetto A AD - Department of Oncology, Unity of Oncological Surgery, Azienda Ospedaliera San Giovanni, Turin, Italy. FAU - Contarini, M AU - Contarini M FAU - Sapino, A AU - Sapino A FAU - Cassoni, P AU - Cassoni P FAU - Consalvo, E AU - Consalvo E FAU - Forno, S AU - Forno S FAU - Pezzi, C AU - Pezzi C FAU - Barnaba, V AU - Barnaba V FAU - Mussa, A AU - Mussa A FAU - Matera, L AU - Matera L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Surg Res JT - The Journal of surgical research JID - 0376340 RN - 0 (Antigens, Neoplasm) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - *Adenocarcinoma MH - Antigen Presentation MH - Antigens, Neoplasm/*immunology MH - Carcinoma, Signet Ring Cell MH - *Colorectal Neoplasms MH - Dendritic Cells/*immunology MH - Humans MH - Interferon-gamma/immunology/metabolism MH - Interleukin-12/pharmacology MH - *Stomach Neoplasms MH - T-Lymphocytes, Cytotoxic/drug effects/immunology/metabolism MH - Tumor Cells, Cultured/cytology/immunology EDAT- 2001/08/23 10:00 MHDA- 2001/09/21 10:01 CRDT- 2001/08/23 10:00 PHST- 2001/08/23 10:00 [pubmed] PHST- 2001/09/21 10:01 [medline] PHST- 2001/08/23 10:00 [entrez] AID - S0022-4804(01)96158-X [pii] AID - 10.1006/jsre.2001.6158 [doi] PST - ppublish SO - J Surg Res. 2001 Sep;100(1):32-8. doi: 10.1006/jsre.2001.6158.