Cross-reactions between tumor cells and allogeneic normal tissues. inhibition of a syngeneic lymphoma outgrowth in h-2 and non-h-2 alloimmune balb/c mice (original) (raw)
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Cancer Immunology Immunotherapy, 1988
In 54 patients with lung and 14 with ovarian carcinomas the quantitative variations of the major histocompatibility complex (MHC)-determined class I and class II antigens of the tumor cells were related to their in vitro interaction with blood lymphocytes, to the lymphoid infiltration of the tumors, and to the metastatic state of the disease. The tumor cell-lymphocyte interaction was measured by the proliferative response in mixed lymphocyte tumor cell culture and by the cytotoxic activity of the lymphocytes. The results showed that (1) none of the 23 tumors from patients with disseminated disease were lysed; (2) class I-negative tumors were not damaged; (3) lymphoid infiltration was present in a higher proportion of class IIpositive tumors; and (4) both MHC-positive and-negative tumors were found among the disseminated tumors. The requirement of class I expression in the lytic interaction substantiates our earlier conclusion concerning the cytotoxic T lymphocyte nature of lymphocyte-mediated autotumor lysis. The lack of auto-tumor lysis in patients with metastases suggests impairment of lymphocyte function in advanced stages of the disease.
Cellular Immunology, 1991
In previous studies, the murine SaI (A/J derived, Kk@ sarcoma was transfected with the allogeneic MHC class I H-2Kb gene, and expressed high levels of H-2Kb antigen. Contrary to expectations, the tumor cells expressing the alloantigen (SKB3. IM tumor cells) were not rejected by autologous A/J mice. Because these results contradict the laws of transplantation immunology, the present studies were undertaken to examine the immunogenicity of SKB3.1M and SaI cells in allogeneic hosts. Similar to SKB3.1 M, SaI cells are lethal in some allogeneic strains, despite tumor-host MHC class I incompatibilities. Tumor challenges of SKB3.1M and SaI cells, however induce MHC class I-specific antibodies and CTL in both tumor-resistant and -susceptible hosts. Although the tumors induce specific CTL, tumor cells are not lysed in vitro by these CTL, suggesting that the tumor cells are resistant to CTL-mediated lysis. Since growth of these tumors does not follow the classical rules of allograft transplantation, and because the tumor is not susceptible to CTL-mediated lysis, we have used Winn assays to identify the effector lymphocyte(s) responsible for SaI rejection. Depletion studies demonstrate that the effector cell is a CD4-CD8+ T lymphocyte. Collectively these studies suggest that the host's response to MHC class I alloantigens of SKB3.1 M and SaI cells does not determine tumor rejection, and that effector cells other than classically defined CTL, but with the CD4-CD8+ phenotype, can mediate tumor-specific immunity. o 1991 Academx
European journal of cancer, 1981
Novel transplantation antigens have been detected in a Moloney virusinduced LSTRA lymphoma of BALB/c origin (H-2a), or in a chemically-induced L5178Y lymphoma of DBA/2 origin, following treatment of tumor-bearing hosts with 5-(3, 3'-dimethyl-l-triazeno-)-imidazole-4-carboxamide (D TIC), for 4-8 transplant generations. Marked cell-mediated cytotoxic responses against D TIC-treated LSTRA or L5178Y lines were found by primary in vivo and secondary in vitro sensitization of histocompatible mice. Moreover, preliminary data show that no obvious antigenic crossreactivity can be found among D TIC-treated sublines derived from distinct parental lymphomas. To test whether D TIC lbzes would express variable levels of normal histocompatibility antigens, cytotoxic lymphocytes were generated in vitro against alloantigens of H-2 complex or sub-regions of it and tested against parental or D TIC'treated lymphomas in a short-term 51Cr-release assay. A col&inhibition test was performed with LSTRA or 4 LSTRA/DTIC sublines. The results showed that little or no difference in the expression of H-2 antigens recognized by cytotoxic lymphocytes could be detected between parental and D TIC-treated sublines. Moreover, no foreign H-2 specificities of H-2 b or H-2 k haplotypes detectable by cytotoxic lymphocytes could have been found in L5178Y or L5178Y/D TIC lymphomas.
Effect of tumor cells on the generation of cytotoxic T lymphocytes in vitro
European Journal of Immunology, 1977
Medi-lCenter. Dumam'and lmmunolow Effect of tumor cells on the generation of cytotoxic T lymphocytes in vitro 1. Accessorv cell functions of mouse tumor cells in the Division of Immunology, Duke University generation of cytotoxic T lymphocytes in vitro: replacement of adherent phagocytic cells by tumor cells Branch, National Cancer Institute, National Institutes of Health, Bethesda' or 2-mercaptoethanol* In agreement with previous reports, the primary in vitro response to alloantigens has been shown t o be dependent o n the presence of m a c r e phages (Mphs). Splenocytes extensively depleted of adherent phagocytic cells did not generate cytotoxic T lymphocytes, and this activity could be completely restored by small numbers of adherent peritoneal cells (accessory cells). Either P388D1 (Mph-like tumor), P388 ("null" tumor) or P8 15 (mastocytoma) tumor cells, or 2-mercaptoethanol, could completely replace the accessory function normally mediated by accessory cells. These tumor cells did not nonspecifically "enhance" the cytotoxic activity generated with normal nondepleted spleen cells. The restored cultures maintained killing specificity t o H-2 targets which was mediated by effector T cells as shown by sensitivity t o anti-@ and complement. Therefore, Mphs seem not t o be the sole cells capable of mediating an accessory function in a primary response t o alloantigens in vitro.
Clinical & Experimental Metastasis, 1994
We have previously found that an increased tumorigenicity and spontaneous metastatic potential of BW5147-derived T lymphoma cells was associated with a decrease in major histocompatibility complex (MHC) class I H-2K k antigen expression. This suggested that H-2K k antigens may control the tumorigenic potential of BW T lymphoma cells. Our current experiments aimed to prove this association by specifically altering H-2K k expression by gene transfection. Transfected cells expressing a high level of H-2K k antigens were significantly less tumorigenic and metastatic after subcutaneous inoculation. However, there was selection in vivo for cells expressing a reduced level of H-2K k antigens, which concomitantly led to an increased tumorigenicity. These data further confirmed the strong association between H-2K k expression and tumorigenicity. We subsequently tested whether the immune system is implicated in this phenomenon by inoculating the H-2K k transfectants into irradiated, immunocompromised recipients. Our results indicate that the reduced tumorigenicity of the BW H-2K k transfectants is due to an immune rejection mechanism, mediated by CD8 § immune effector cells, as revealed by in vivo depletion experiments with anti-CD8 antibodies. Hence, we hereby demonstrated that H-2K k antigens increased the immunogenicity of BW cells, via a CD8-dependent mechanism, which consequently reduced their tumorigenicity.
Untreated or drug-treated tumor cells are differentially recognized by allogeneic lymphocytes
International Journal of Immunopharmacology, 1994
Murine tumor cells treated with triazene compounds (TZC), in vivo or in vitro, are capable of eliciting specific transplantation resistance in syngeneic hosts, and T-cell-mediated proliferative and cytotoxic responses, directed against novel drug-induced antigen(s). Since this phenomenon, referred to as chemical xenogenization (CX)could open up new perspectives in the immunochemotherapy of human neoplasias, it was of interest to investigate whether CX could also occur in human tumors. However, established human tumor cell lines along with fully immunocompetent autologous lymphocytes, are seldom available. Therefore studies were carried out to test whether parental or TZC-treated tumor cells could be differentially recognized by allogeneic lymphocytes. Experiments were performed in both human and murine models, using a lung adenocarcinoma line treated in vitro with TZC, or an established xenogenized mouse lymphoma, respectively. The results indicate that allogeneic cytotoxic T-lymphocytes (CTL) recognize specifically murine TZC-treated tumor cells, This was supported by the finding that antisera directed against the drug-treated cells abrogated the generation and the cytolytic activity of allogeneic CTL reactive against the TZC-treated tumor. In addition it was found that changes of the antigenic pattern of cell membrane recognizable by cloned allogeneic CTL occur in the TZC-treated human carcinoma cell line.