Tumor-infiltrating lymphocytes (TIL) were isolated from 40 of 51 consecutive human liver tumor samples (primary hepatocellular carcinoma, 16 of 18; metastatic, 23 of 29; benign, one of four). Functional and phenotypic characteristics of fresh and recombinant interleukin-2 (rIL-2)-expanded TIL were evaluated. The expansion of TIL from hepatic tumors in the presence of 1000 units/ml of rIL-2 was possible in 60% of cases. In comparison to TIL from metastatic liver tumors, TIL obtained from primary liver tumors expanded faster and better in rIL-2 cultures. Expanded TIL from primary tumors had significantly higher cytotoxicity against K562 targets, but not Raji targets, than those from metastatic tumors. Cytotoxicity against fresh autologous tumor targets was detected in seven of eight cultures tested. TIL from primary tumors retained antitumor reactivity significantly longer in culture. The optimal in vitro cytotoxicity was achieved between days 20 and 60 of culture in the presence of rIL-2. Antitumor activity was associated with the increase in these TIL cultures of a cell population expressing the Leu19 antigen with or without the CD3 antigen. The frequency of the CD3+Leu19+ population showed a bimodal distribution during culture: the first peak of CD3+Leu19+ cells occurred between days 30 and 60 and was associated with the increased antitumor activity; the second peak occurred after day 60 and was not associated with activity. These findings demonstrate that TIL from most human hepatic tumors can be successfully isolated, cultured in rIL-2, and enriched in Leu19+ effectors. In addition, these TIL upon IL-2 activation in vitro are capable of lysing fresh autologous and/or allogeneic tumor targets.
Lymphocytes infiltrating human solid tumors (TIL) and autologous peripheral blood lymphocytes (A-PBL) were cultured with 1000 units/ml of recombinant interleukin 2 (rIL2) in long-term cultures. TIL isolated from 26 primary squamous cell carcinomas of the head and neck expanded better (P less than 0.01) and achieved higher total lytic units of activity against fresh tumor cell targets (P less than 0.05) than A-PBL. TIL obtained from primary hepatocellular carcinomas (n = 7) showed a higher degree of expansion than those from metastatic liver tumors (n = 7). Further, TIL from metastatic tumors of the head and neck, liver, and ovary were delayed up to 50 days in their proliferative response to rIL2. Long-term mass cultures in rIL2 of TIL, A-PBL, or normal PBL were serially monitored for cytotoxicity with different cultured and fresh tumor cell targets and for phenotypic markers of the predominating cell populations. Antitumor cytotoxicity was found in cultures enriched in CD3+Leu19+ and/or CD3-Leu19+ cells. Two-color sorting of such cultures followed by cytotoxicity assays confirmed that the human antitumor effectors expressed either the CD3+Leu19+ or CD3-Leu19+ phenotype. CD3+Leu19- cells had little or no antitumor cytotoxicity. The two types of Leu19+ effector cells were present in low numbers in fresh TIL, A-PBL, or normal PBL; in contrast, in some rIL2-expanded long-term cultures, they represented a majority of proliferating cells. This study identifies for the first time two types of antitumor effector cells in rIL2 cultures of human TIL, one of which may represent activated natural killer cells on the basis of the absence of the CD3 and expression of the Leu19 antigen. These antitumor effector cells mediate non-MHC-restricted cytotoxicity of fresh or cultured tumor cell targets of different histologic types.
We evaluated 56 consecutive patients with newly diagnosed lymphoma including 48 with non-Hodgkin's lymphoma (NHL) and 8 with Hodgkin's disease to determine the clinical and prognostic significance of magnetic resonance imaging (MRI) of the femoral marrow. MR images of the femoral marrow were obtained by the T1-weighted spin echo method and the short TI inversion recovery technique. Abnormal “positive” images were seen in 29 of the 56 patients (52%). All 17 patients with positive biopsy results showed abnormal images on their femoral marrow MRI. Three “positive” MRI patterns — scattered (72%), uniform (21%), and nodular (7%) — were observed. The overall survival of the patients with a positive MRI pattern was significantly poorer than that of patients with a normal pattern (P = .0129). Survival did not differ significantly according to MRI pattern. The 3-year survival rate in the patients with a normal MRI pattern was 89.9% and in the patients with a positive MRI pattern, it was 41.0%. This difference was statistically significant (P = .0279) when we evaluated only the patients with NHL. Patients with positive MRI patterns, but a normal bone marrow histology, showed a significantly shorter survival than those with a normal MRI pattern (P = .016). These results indicate that abnormal MR images of the femoral marrow are associated with a significantly poorer survival in patients with malignant lymphoma, regardless of histologic findings in the marrow.
We investigated the effects of tertiary amine local anesthetics (procaine and lidocaine), which are proposed to effect the plasma membrane, on human natural killer (NK) cells.NK cell activity against K-562 was measured in a 4 h-51Cr release assay. Procaine and lidocaine markedly inhibited human NK cell activity in a dose dependent manner. The inhibition was prompt and irreversible. Procaine inhibited not only the binding, but also NK cell activity when NK cells were preincubated with procaine before K-562 cells were added, whereas procaine inhibited NK cell activity without interfering with the binding when it was added after the binding was completed. These findings suggest that the plasma membrane, possibly phospholipids, may play an important role for human NK cells to bind to and kill the target cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.