TY - JOUR
T1 - Frequency of cytotoxic T lymphocyte precursors (CTLp) interacting with autologous tumor via the T-cell receptor
T2 - Limiting dilution analysis of specific CTLp in peripheral blood and tumor-invaded lymph nodes of melanoma patients
AU - Mazzocchi, A.
AU - Belli, F.
AU - Mascheroni, L.
AU - Vegetto, C.
AU - Parmiani, G.
AU - Anichini, A.
PY - 1994
Y1 - 1994
N2 - The frequencies of cytotoxic T-lymphocyte precursors (CTLp) that lyse autologous tumor by a T-cell receptor (TCR)dependent mechanism (specific CTLp) were evaluated by limiting dilution analysis (LDA) using lymphocytes from peripheral blood (PBL) and from surgically resected, tumor-invaded lymph nodes (LNL) in 9 melanoma patients. The frequency of specific CTLp was determined in PBLs and/or LNIs of all patients by a modified LDA assay, enabling us to measure lytic activity on the autologous tumor that could be significantly inhibited by an anti-CD3 monoclonal antibody (MAb). This assay allowed us to detect frequencies of specific CTLp ranging from 1/720 to 1/32,037 in peripheral blood and from 1/328 to 1/22,061 in tumor-invaded lymph nodes. These frequencies indicated that lymphoid populations from PBLs or LNLs of melanoma patients may contain as low as 30 to as much as 3,000 specific CTLp/106 lymphocytes. In addition, comparison of wells containing specific CTLp with those showing no inhibition by anti-CD3 MAb indicated that specific CTLp represent between 3 and 88% of all precursors with lytic activity on the tumor. In 6 of 9 patients, no marked differences between PBLs and LNIs in specific CTLp frequencies were found. A 10-fold increase of specific CTLp, in comparison to PBL and LNL, was found only in lymphocytes isolated from a subcutaneous metastasis of one patient. Our results indicate that CTLp interacting with autologous tumor by a TCR-dependent mechanism exist in PBL and LNL of most melanoma patients, although a wide variation in their absolute number is evident among different patients.
AB - The frequencies of cytotoxic T-lymphocyte precursors (CTLp) that lyse autologous tumor by a T-cell receptor (TCR)dependent mechanism (specific CTLp) were evaluated by limiting dilution analysis (LDA) using lymphocytes from peripheral blood (PBL) and from surgically resected, tumor-invaded lymph nodes (LNL) in 9 melanoma patients. The frequency of specific CTLp was determined in PBLs and/or LNIs of all patients by a modified LDA assay, enabling us to measure lytic activity on the autologous tumor that could be significantly inhibited by an anti-CD3 monoclonal antibody (MAb). This assay allowed us to detect frequencies of specific CTLp ranging from 1/720 to 1/32,037 in peripheral blood and from 1/328 to 1/22,061 in tumor-invaded lymph nodes. These frequencies indicated that lymphoid populations from PBLs or LNLs of melanoma patients may contain as low as 30 to as much as 3,000 specific CTLp/106 lymphocytes. In addition, comparison of wells containing specific CTLp with those showing no inhibition by anti-CD3 MAb indicated that specific CTLp represent between 3 and 88% of all precursors with lytic activity on the tumor. In 6 of 9 patients, no marked differences between PBLs and LNIs in specific CTLp frequencies were found. A 10-fold increase of specific CTLp, in comparison to PBL and LNL, was found only in lymphocytes isolated from a subcutaneous metastasis of one patient. Our results indicate that CTLp interacting with autologous tumor by a TCR-dependent mechanism exist in PBL and LNL of most melanoma patients, although a wide variation in their absolute number is evident among different patients.
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U2 - 10.1002/ijc.2910580304
DO - 10.1002/ijc.2910580304
M3 - Article
C2 - 8050813
AN - SCOPUS:0028068922
VL - 58
SP - 330
EP - 339
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 3
ER -