Autochthonous Tumor Cells Research Articles

Abstract 4574: A novel method for inactivating tumor cells for use in a personalized cancer vaccine

Abstract With the recent interest in personalized medicine for cancer patients and immune therapy, the field of cancer vaccines has been resurrected. Previous autologous, whole cell tumor vaccine trials have not produced convincing results due, in part, to poor patient selection and inactivation methods that are harsh on the cells. Such methods can inadvertently alter protein structure and antigenic profile in ways that make vaccine candidates ineffective in stimulating immune response to autochthonous tumor cells. We decided to investigate a novel method for inactivating tumor cells that uses UVA/UVB light and the benign chemical riboflavin (Riboflavin and UV Light Inactivation, RF+UV). This process is fast and results in complete inactivation of the tumor cells, but preserves tumor cell integrity and antigenicity due to its rapid, yet gentle inactivation process. Our results demonstrate that the inactivation is complete, that proteins are preserved on the surface of the tumor cells, and that the inactivated tumor cells are immunogenic in that they induce dendritic cell maturation, increased IFNγ production, and the generation of tumor cell-specific IgG immune responses. Moreover, when formulated with an adjuvant (“Innocell vaccine”) and tested in two different murine primary tumor models and one metastatic tumor model, the vaccine led to decreased tumor growth, prolonged survival and decreased metastatic disease. In addition, immune cells obtained from tumor tissue following vaccination showed a decrease in exhausted and regulatory cells, suggesting that activation of intratumoral T cells may be playing a role leading to the reduce tumor growth. Lastly, tumor tissue was obtained from 3 client-owned dogs with spontaneous tumors and used to generate an autologous Innocell vaccines. The vaccine was well-tolerated and induced an inflammatory response in 2 of the 3 dogs. This data suggests that the RF+UV process of inactivating tumor cells for use as antigen-presenting agents in cancer vaccine therapy may provide a more rapid, safer and gentler way to generate autologous whole tumor cell vaccines for use in cancer patients. Citation Format: Amanda Michele Guth, Raymond Goodrich, Haemin Park, Matthew Gladstone, Crystal Shanley, Lindsay Hartson, Jon Weston. A novel method for inactivating tumor cells for use in a personalized cancer vaccine [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4574.

A novel cancer immunotherapy utilizing autologous tumour tissue.

With the recent interest in personalized medicine for cancer patients and immune therapy, the field of cancer vaccines has been resurrected. Previous autologous, whole cell tumour vaccine trials have not produced convincing results due, in part to poor patient selection and inactivation methos that are harsh on the cells. These methods can alter protein structure and antigenic profiles making vaccine candidates ineffective in stimulating immune response to autochthonous tumour cells. We investigated a novel method for inactivating tumour cells that uses UVA/UVB light and riboflavin (vitamin B2) (RF+UV). RF+UV inactivates the tumour cells' ability to replicate, yet preserves tumour cell integrity and antigenicity. Our results demonstrate that proteins are preserved on the surface of RF+UV-inactivated tumour cells and that they are immunogenic via induction of dendritic cell maturation, increase in IFNγ production and generation of tumour cell-specific IgG. Moreover, when formulated with an adjuvant ('Innocell vaccine') and tested in different murine tumour primary and metastatic disease models, decreased tumour growth, decreased metastatic disease and prolonged survival were observed. In addition, immune cells obtained from tumour tissue following vaccination had decreased exhausted and regulatory T cells, suggesting that activation of intra-tumoural T cells may be playing a role leading to reduced tumour growth. These data suggest that the RF+UV inactivation of tumour cells may provide an efficacious method for generating autologous whole tumour cell vaccines for use in cancer patients.

Abstract 4629: FOXA2 controls tumor-associated inflammation inKRAS-mutant lung cancer

Abstract Background: Although the role of the transcription factor FOXA2 in lung cancer has been investigated using mouse and human lung cancer cell lines, to our knowledge, the role of FOXA2 in autochthonous lung tumors in GEMM (Genetically Engineered Mouse Model) has not been determined. Methods: In order to determine the role of FOXA2 in autochthonous lung tumor cells, we deleted FOXA2 in lung epithelia of Kras-mutant lung cancer model mice (Scgb1a1-Cre;[tetO]-Kras4bG12D;Foxa2flox/flox, a GEMM) and assessed survival and lung histology of the GEMM. Results: Deletion of FOXA2 in autochthonous Kras-mutant lung tumor cells significantly extended the survival of Kras-mutant lung cancer model mice (median survival from 8 weeks to 23 weeks; n>14 for each group). Histological analysis indicated that FOXA2 was required for the growth of lung tumor cells and the recruitment of tumor-associated macrophages. Conclusion: FOXA2 promotes primary KRAS-mutant lung tumors in part by controlling tumor-associated inflammation. Citation Format: Koichi Tomoshige, Minzhe Guo, Iris Fink-Baldauf, William Stuart, Yutaka Maeda. FOXA2 controls tumor-associated inflammation inKRAS-mutant lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4629.

Abstract 4791: Inhibition of Tumor Formation in Mice following Vaccination with DNA Encoding a Novel Xenogeneic Tumor Associated Auto-Antigen

Abstract Tumor protein D52 (TPD52) is a novel auto-antigen involved in cellular transformation, proliferation and metastasis. Its over-expression has been demonstrated in several human malignancies including prostate, breast, and ovarian carcinomas. Murine TPD52 (mD52) has been shown to induce anchorage independent growth in vitro and spontaneous metastasis in vivo. Importantly, mD52 mirrors the function and normal tissue expression patterns of the human orthologue of TPD52 (hD52) and shares 86% identity at the amino acid level. Thus, TPD52 represents a self, non-mutated tumor associated auto-antigen that is important for maintaining a tumorigenic phenotype. The Transgenic Adeno-carcinoma of the Mouse Prostate (TRAMP) model was employed to study TPD52 as a vaccine antigen. Naïve mice were immunized with either mD52 or hD52 DNA. Following immunization, mice were challenged with a subcutaneous, tumorigenic dose of mD52 positive, autochthonous TRAMP-C1 tumor cells. Greater than 70% of mice were tumor free more than 10 months post tumor challenge when immunized with hD52 as a xenogenic DNA vaccine. Survivors of the initial tumor challenge rejected a second tumor challenge with TRAMP-C2 tumor cells given in the opposite flank approximately 138 days after the first challenge with TRAMP-C1, and remained tumor free for more than 6 months. The T cell cytokine secretion patterns from tumor challenge survivors indicated that a cellular immune response was involved in tumor rejection. These data suggest that hD52 xenogeneic DNA vaccination induced a memory, cellular immune response that resulted in superior protection from challenge with murine prostate-derived tumors that naturally over-express mD52 protein. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4791.

Memory and cellular immunity induced by a DNA vaccine encoding self antigen TPD52 administered with soluble GM-CSF.

Tumor protein D52 (TPD52) is involved in cellular transformation, proliferation and metastasis. TPD52 over expression has been demonstrated in several cancers including prostate, breast, and ovarian carcinomas. Murine TPD52 (mD52) has been shown to induce anchorage independent growth in vitro and metastasis in vivo, and mirrors the function and normal tissue expression patterns of the human orthologue of TPD52. We believe TPD52 represents a self, non-mutated tumor associated antigen (TAA) important for maintaining a transformed and metastatic cellular phenotype. The transgenic adeno-carcinoma of the mouse prostate (TRAMP) model was employed to study mD52 as a vaccine antigen. Naïve mice were immunized with either recombinant mD52 protein or plasmid DNA encoding the full-length cDNA of mD52. Following immunization, mice were challenged with a subcutaneous, tumorigenic dose of mD52 positive, autochthonous TRAMP-C1 tumor cells. Sixty percent of mice were tumor free 85 days post challenge with TRAMP-C1 when immunized with mD52 as a DNA-based vaccine admixed with soluble granulocyte-macrophage colony stimulating factor (GM-CSF). Survivors of the initial tumor challenge rejected a second tumor challenge given in the opposite flank approximately 150 days after the first challenge, and remained tumor free for more than an additional 100 days. The T cell cytokine secretion patterns from tumor challenge survivors indicated that a T(H)1-type cellular immune response was involved in tumor protection. These data suggest that mD52 vaccination induced a memory, cellular immune response that resulted in protection from murine prostate tumors that naturally over express mD52 protein.

Memory and protective cellular immunity induced by the murine orthologue of metastasis associated protein TPD52 (B155)

Abstract Tumor protein D52 (TPD52) is involved in tumor cell proliferation, trafficking and metastasis. TPD52 over expression has been demonstrated in prostate, breast, lung and colon carcinomas. Murine TPD52 (mD52) has been shown to induce transformation and metastasis, and mirrors the known function and expression patterns of the human orthologue. We believe TPD52 represents a self, non-mutated tumor associated antigen (TAA) with direct relevance to human cancers. The Transgenic Adeno-carcinoma of the Mouse Prostate (TRAMP) model was employed to study mD52 as a vaccine antigen. Naïve mice were immunized with plasmid DNA encoding the full length cDNA of mD52. Following the final immunization, mice were challenged s.c. with a tumorigenic dose of mD52 positive, autochthonous TRAMP-C tumor cells. Greater than 60% of mice were tumor free 85 days post challenge with TRAMP-C1 and 40% were tumor free post challenge with TRAMP-C2 tumor cells, without induction of observable autoimmunity. Survivors of TRAMP-C2 initial tumor challenge rejected a second TRAMP-C2 tumor challenge 73 days later and remained tumor free greater than 90 days. The T cell cytokine secretion patterns from tumor challenge survivors indicated that a TH1 cellular immune response was involved in tumor rejection. These data suggest that mD52 vaccination induced a memory immune response that resulted in rejection of mD52+ tumors without inducing autoimmunity.

814 poster Particular focus in long term survivors with primary historical immunotherapy experience in stage III/IV melanoma using non autochthonous irradiated tumor cells

814 poster Particular focus in long term survivors with primary historical immunotherapy experience in stage III/IV melanoma using non autochthonous irradiated tumor cells

Two tumor models of curative adoptive chemoimmunotherapy using tumor-infiltrated spleen cells with potent antitumor cytotoxicity stimulated by antigen-sharing tumors.

Previously we have established curative protocols for adoptive chemoimmunotherapy (ACIT) of mice bearing different plasmacytomas that are known to bear cross-reacting antigens: (a) the cure of mice bearing an early-stage, nonpalpable MOPC-315 tumor by a very low dose of cyclophosphamide (10 mg/kg) and cultured MOPC-315-tumor-infiltrated (TI) spleen cells (25 x 10(6)) and (b) the cure of mice bearing a late-stage, relatively drug-resistant, highly metastatic RPC-5 tumor with cyclophosphamide (100 mg/kg) and cultured RPC-5 TI spleen cells (25 x 10(6) - 50 x 10(6)). In both models, the spleen cells were obtained from mice bearing a late-stage tumor and were cultured for 5 days in the presence of polyethyleneglycol 6000 and autochthonous tumor cells as a source of tumor antigen. Here we show that RPC-5 tumor cells could substitute for MOPC-315 tumor cells in the 5-day culture of MOPC-315 TI spleen cells so that they became curative in ACIT for mice bearing an early-stage MOPC-315 tumor. Similarly, MOPC-315 tumor cells could substitute for RPC-5 tumor cells in the 5-day culture of RPC-5 TI spleen cells so that they became curative in ACIT of mice bearing a late-stage RPC-5 tumor. In addition, RPC-5 TI spleen cells cultured with either MOPC-315 or RPC-5 tumor cells were effective in curing all mice bearing an early-stage MOPC-315 tumor by ACIT. However, MOPC-315 TI spleen cells whether cultured with MOPC-315 or RPC-5 tumor cells, were much less effective than cultured RPC-5 TI spleen cells in curing mice bearing a late-stage RPC-5 tumor by ACIT (although the survival of these mice was extended significantly). Interestingly, whereas RPC-5 TI spleen cells cultured with either MOPC-315 or RPC-5 tumor cells were as effective as MOPC-315 TI spleen cells cultured under the same conditions in lysing MOPC-315 tumor cells in vitro, MOPC-315 TI spleen cells that had been cultured with either MOPC-315 or RPC-5 tumor cells exerted a much weaker in vitro cytotoxic T lymphocyte activity against RPC-5 tumor cells than did RPC-5 TI spleen cells that had been cultured under the same conditions.

In vitro and in vivo growth and casein gene expression of mouse mammary tumor epithelial cells in response to hormones

Cells from autochthonous mouse mammary carcinomas which display estrogen-independent growth vivo were studied for their hormonal responses in primary culture. A culture system employing insulin-supplemented, serum-free medium and basement membrane Matrigel as a substratum was used to cultivate tumor cells. The cells did not exhibit in vitro estrogenor prolactin-dependent growth. Primary tumors still displayed a constitutional expression of α-, β-, and γ-casein mRNAs. These messages were dramatically reduced during the culture period. However, seven to eightfold increases in α- and β-casein mRNAs were inducible in the 5-day cultures by treatment with prolactin and hydrocortisone. If the hormones were present through a 2-week culture period, the levels of α-, β-, and γ-casein mRNAs in the cells were maintained and displayed in a time-dependent increase with a peak at 10–14 days. The accumulation of β-casein mRNA in vitro did not require DNA synthesis. Administration of prolactin directly into the growing tumors in vivo could also enhance β-casein mRNA levels in the tumor cells. Morphological studies of the cells cultured in the presence of prolactin and hydrocortisone did not reveal visible changes compared with those without hormonal treatment. Transplantation of tumor cells cultured in the presence or absence of hormones resulted in the development of tumors in mice at approximately the same time. The current studies suggest that the autochthonous mammary tumor cells, independent of estrogen for cell growth, were still inducible for casein gene expression in vitro and in vivo by appropriate hormones. The induction and maintenance of casein messages by a single hormonal treatment did not appear to correlate with morphology and DNA synthesis of cells in vitro or with tumor-producing capacities in vivo.

Immunohistochemical and in Vitro Functional Analysis of Pineal-Germinoma Infiltrating Lymphocytes: Report of a Case

Abstract The present study describes the phenotypic and functional analysis of tumor-infiltrating lymphocytes isolated from a germinoma located in the pineal region. Tumor-infiltrating lymphocytes were separated from the germinoma and cultured in medium containing IL-2 (1000 U/ml). An immunohistochemical analysis of frozen sections revealed that 90% of the germinoma-infiltrating lymphocytes were CD3-positive T cells expressing CD4, CD8, and HLA Class I and Class II antigens, but were negative for CD16, CD20, CD23, CD25 and CD14 antigens. After in vitro cultivation in the presence of high concentrations of IL-2, the lymphocytes proliferated for 2 weeks, showing marked DNA synthesis. In addition, the lymphocytes could lyse NK-resistant allogeneic target cells. These results provide evidence for a potential role of germinoma-infiltrating lymphocytes in vivo, and suggest that the lymphocytes may control the growth of autochthonous tumor cells by killing those that are not restricted to the major histocompatibility complex.

Isolation and Characterization of Growth Factor(s) From a Human B-Cell Lymphoma

We demonstrate that human neoplastic B cells (Br cells) contain a cytoplasmic protein of molecular mass 60 Kd that exhibits B-cell growth factor (BCGF) activity on growth factor-dependent long-term human B cells as well as on autochthonous tumor cells. This 60-Kd protein is recognized by antibodies against a similar intracellular 60-Kd protein derived from normal human lymphocytes. These results demonstrate that the two proteins share epitope homology. Microculture bioassays indicate that neoplastic and normal 60-Kd proteins are capable of driving neoplastic B cells through S-phase. Western immunoblot analysis indicates that neoplastic B cells secrete 60- as well as 14-Kd protein. Immunoaffinity-purified proteins secreted by Br cells exhibit BCGF activity in anti-IgM or dextran sulfate-preactivated human B cells. In addition, a double-antibody immunofluorescence staining technique was used to demonstrate that Br cells express cell surface receptors for BCGF molecule(s). These studies provide support for the autocrine growth model for neoplastic human B cells and suggest that the autocrine growth factor derived from such tumor cells is similar if not identical to normal BCGF molecules.

Isolation and characterization of growth factor(s) from a human B-cell lymphoma

We demonstrate that human neoplastic B cells (Br cells) contain a cytoplasmic protein of molecular mass 60 Kd that exhibits B-cell growth factor (BCGF) activity on growth factor-dependent long-term human B cells as well as on autochthonous tumor cells. This 60-Kd protein is recognized by antibodies against a similar intracellular 60-Kd protein derived from normal human lymphocytes. These results demonstrate that the two proteins share epitope homology. Microculture bioassays indicate that neoplastic and normal 60-Kd proteins are capable of driving neoplastic B cells through S-phase. Western immunoblot analysis indicates that neoplastic B cells secrete 60- as well as 14-Kd protein. Immunoaffinity-purified proteins secreted by Br cells exhibit BCGF activity in anti-IgM or dextran sulfate-preactivated human B cells. In addition, a double-antibody immunofluorescence staining technique was used to demonstrate that Br cells express cell surface receptors for BCGF molecule(s). These studies provide support for the autocrine growth model for neoplastic human B cells and suggest that the autocrine growth factor derived from such tumor cells is similar if not identical to normal BCGF molecules.

Isolation and in vitro growth of glioma-infiltrating lymphocytes, and an analysis of their surface phenotypes.

The present investigation was conducted in order to examine the feasibility of isolating and growing glioma-infiltrating lymphocytes in vitro as possible effector cells for use in new adoptive immunotherapy. Eight surgical specimens obtained from patients with malignant astrocytomas were treated by enzyme dispersion; the cells were separated on a density gradient and grown in the presence of human recombinant interleukin-2. The cultured lymphocytes were tested for cell-surface markers by using monoclonal antibodies in a flow cytometric analysis. In all cases the glioma-derived lymphocytes were grown in culture for several weeks with substantial increases in cell numbers (at least 5 X 10(8) cells). The mature T cell population (CD3, 89%) was found to have an increased proportion of the cytotoxic/suppressor phenotype CD8 (55%) as compared to peripheral blood lymphocytes (PBL's). Eighty-six percent of the cultivated lymphocytes expressed HLA-DR. The IL-2 receptor was predominantly expressed on the helper subset (CD4-positive). Otherwise, anti-CD16, which specifically reacts with natural killer (NK) cells, did not stain significantly more of the cultured gliomaderived lymphocytes compared with lymphocyte-activated PBL's. These results corroborate the observations made with conventional immunohistochemical examination. It has been demonstrated that T lymphocytes isolated from human cancers are enriched for specific reactivity to their autochthonous tumor cells. These experiments support the possible use of glioma-infiltrating lymphocytes as a new treatment for patients with malignant glioma.

Biologic Characterization of Human Bone Tumors: IX. Occurrence of macrophages

Fifty bone tumors were investigated using immunohistological methods for an assessment of the amount and nature of macrophage infiltration. Polyclonal antibodies against lysozyme, alpha 1-antichymotrypsin, and alpha 1-antitrypsin were used as markers, besides certain monoclonal antibodies against blood monocytes and mature tissue macrophages. Particularly high macrophage infiltration was found in malignant fibrous histiocytomas, giant cell-containing osteosarcomas, giant cell tumors of bone, and aneurysmal bone cysts. Moderate infiltrates were seen in some highly malignant osteosarcomas, in fibrosarcoma, and in chondroblastoma. A low macrophage content was observed in some osteosarcomas, in Ewing's sarcomas, chordomas, fibrous dysplasias, aggressive fibromatoses, and cartilage tumors. Osteoclast-like giant cells showed distinctly positive reactions with the monoclonal antibody against mature tissue macrophages. In fibrohistiocytic tumors (MFH, giant cell tumor, non-ossifying fibroma) only macrophages gave positive reactions with those antibodies, whereas the reaction of spindle-shaped tumor cells was always negative. These results strongly indicate that the macrophages found in bone tumors (including those of fibrohistiocytic type) result from reactive infiltration. The autochthonous tumor cells are most probably derived from local mesenchymal cells, and are thus cytogenetically unrelated to the infiltrating macrophages.

The immune reactivity of the regional and distant lymph nodes to autochthonous ovine squamous cell carcinomata

Anti-tumor immune reactivity of lymphocytes derived from lymph nodes regional to and distant from tumor growth, as well as that of peripheral blood leucocytes, against autochthonous tumor cells, was investigated. Experiments were carried out in vitro using a 51Cr cytotoxic assay and in vivo by cannulating the afferent and efferent lymphatics of regional and distant lymph nodes and challenging via the afferent lymphatics with 10 7 cultivated autochthonous tumor cells. No anti-tumor cytotoxic reactivity was detected in vitro using lymphocytes derived from any of the sources studied. In vivo , while challenge with autochthonous tumor cells produced no response in the regional lymph node, significant blast cell response was obtained in the distant node. The response at the distant node was associated with the production of antibodies that could bind to tumor cells without causing their demise. The anergy observed at the regional lymph node, and the possibility of a relation between the events occurring at that node and those observed at the distant node, are discussed.

Immune reactivity to autochthonous ovine squamous cell carcinomata

The immune reactivity of tumor-bearing sheep to autochthonous tumor cells was investigated in the efferent lymph of a lymph node distant from the primary tumor site. This was done while the primary tumor was in situ and after its resection. The immune response to challenge with tumor cells while the primary tumor was in situ was associated with the detection of antibodies which were specific for the tumor cells but did not cause their demise. However, both humoral and cellular cytotoxic reactivities were detected in the lymph following removal of the primary tumor and rechallenge with tumor cells. This response had the characteristic of a secondary immune reponse which indicates sensitization to tumor antigens by the host. Thus the presence of the primary tumor has interfered with pre-existing host immunity.

Suppression of antitumor immunity by macrophages in spleens of mice bearing a large MOPC-315 tumor.

We had shown previously that progression of MOPC-315 plasmacytoma growth is associated with an increase in the percentage of macrophages in the spleen as well as a decrease in the ability of tumor-bearer spleen cells to mount an antitumor cytotoxic response upon in vitro immunization. Here we provide evidence that macrophages in the MOPC-315 tumor-bearer spleen are responsible at least in part for the suppression of the generation of antitumor cytotoxicity. Accordingly, removal of most macrophages by depletion of phagocytic cells or Sephadex G-10-adherent cells from spleens of mice bearing a large tumor resulted in augmented antitumor immune potential. Also, Sephadex G-10-adherent spleen cells from tumor-bearing (but not normal) mice drastically suppressed the in vitro generation of antitumor cytotoxicity by normal spleen cells. The suppressive activity of these adherent cells did not reside in contaminating suppressor T cells, since it was not reduced by treatment with monoclonal anti-Thy 1.2 antibody plus complement. The Sephadex G-10-adherent cell population from the tumor-bearer spleen suppressed the in vitro generation of antitumor cytotoxicity against autochthonous tumor cells but not against allogeneic EL4 tumor cells, and hence the suppression was apparently specific. The suppressive activity of the Sephadex G-10-adherent cell population from tumor-bearer spleens was overcome by treatment of the tumor-bearing mice with a low curative dose of cyclophosphamide. This immunomodulatory effect of a low dose of the drug in overcoming the suppression mediated by the Sephadex G-10-adherent cell population enables the effector arm of the immune system of tumor-bearing mice to cooperate effectively with the drug's tumoricidal activity in tumor eradication.

Study of Tumor-Associated Blastogenic Reactivity of Peripheral Blood Lymphocytes and Regional Lymph Node Lymphocytes in Human Malignancy

The in vitro blastogenic responses of peripheral blood lymphocytes (PBL) and the regional lymph node lymphocytes (LNL) from cancer patients to autochthonous tumor cells (TC) were investigated. A positive lymphocyte response to autochthonous TC was observed in 23% (6/26) for PBL and 34% (9/26) for LNL. There seemed to be an inverse relationship between PBL and LNL responses to autochthonous TC. There was no significant difference between PBL and LNL responses to autochthonous TC according to the primary site of the tumor. Analysis of PBL and LNL responses to autochthonous TC according to the extent of the disease revealed that LNL were definitely more reactive than PBL in patients with a primary tumor that had not spread to the regional lymph nodes.

The immunological role of the thymus in the pathogenesis of virus-induced lymphomas. Suppression of cytolytic T-cell function

Thymectomy of young adult mice has been found to prevent virus-induced lymphomas which develop as the animals age. Thymectomy protects mice by removing a source of suppressor T cells which inhibit the generation of cytolytic T cells against autochthonous tumors. Furthermore, suppression is specific since T cells are regulated in their capacity to respond to syngeneic but not allogeneic tumor cells. To determine if suppression could be adoptively transferred, lethally irradiated, bone-marrow-reconstituted mice were inoculated with T cells from either normal or thymectomized mice. Only T cells from thymectomized animals transferred enhanced T-cell reactivity to syngeneic tumor cells. More importantly, T cells from thymectomized mice injected with virus protected recipients challenged with lethal doses of syngeneic tumor cells. We conclude that thymectomy protects mice from developing virus-induced T-cell lymphomas by removing a source of suppressor T cells which regulates the activity of specific cytolytic T cells directed against autochthonous tumor cells.

Autochthonous humoral and cellular immunoreactivity to colorectal carcinoma: Prognostic significance in 400 patients

We tested 400 colorectal carcinoma patients preoperatively for serum antibodies to tumor cell cytoplasm and membrane, and for blood lymphocyte cytotoxicity against autochthonous tumor cells and serum blocking. All the patients were followed up postoperatively for 3 months to 8 1/2 years (mean 35 months) and their recurrence-free periods and survival times were assessed. In the 345 patients treated by curative resection a significant favorable association was found between autoantibody to tumor cytoplasm and disease-free survival. In the 55 patients treated by palliative resection there was a correlation between blood lymphocyte cytotoxicity and survival.