Mixed Tumor Challenge of Strain Specific and Nonspecific TA3 Mouse Ascites Mammary Adenocarcinoma

Nowotny, Alois; Grohsman, Jonathan

doi:10.1159/000230950

Cited by 9 publications

(2 citation statements)

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“…The results of Nowotny and Grohsman (140) suggested that the relative proportion of two subpopulations of the TA3 mouse mammary adenocarcinoma, which display one-way cross-reactivity, might dictate whether immune rejection of immunoresistant cells or the escape of immunosensitive cells will occur. Mixtures of the two subpopulations injected into normal mice resulted in either the growth of both lines when the immunoresistant line was in excess, or the rejection of both when the immunosensitive line was in excess.…”

Section: Subpopulation Interactions In Intratumor Immunologic Heterogmentioning

confidence: 99%

Intratumor immunologic heterogeneity

Miller

1982

Cancer Metast Rev

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Tumor cells express a great variety of antigens including tumor specific transplantation antigens, tumor-associated antigens, differentiation antigens, histocompatibility antigens, lectin-binding sites and receptors for natural killer cells and natural antibodies. These antigens are distributed unevenly on tumor subpopulations and each subpopulation may induce different immune responses to the same determinant. Intratumor immunologic heterogeneity arises early in cancer, possibly during preneoplasia, and exists throughout the course of progression. Metastatic subpopulations are not generally less antigenic than subpopulations within primary tumors. Different arrays of antigenic determinants are displayed by subpopulations but variability in cell surface expression of a single determinant is also a fundamental type of immunologic heterogeneity. Antigenic specificity patterns commonly reveal one-way cross-reactions between tumor subpopulations. One-way cross-reactions might occur due to quantitative differences, cell-cycle variations, modulation, masking, H-2 expression and restriction phenomena, or alteration in the carbohydrate side-chains of glycoproteins. Interactions which occur when subpopulations co-exist may alter immune responses so that the response to the mixture is not the sum of the responses to the individual subpopulations. It is suggested that the exploitation of the mechanisms involved in immunologic heterogeneity may lead to new therapeutic approaches and that the great diversity of determinants expressed by tumor cells could lead to development of multivalent panel of monoclonal antisera which, acting synergistically, could preferentially lyse tumor cells.

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Section: Subpopulation Interactions In Intratumor Immunologic Heterogmentioning

confidence: 99%

Intratumor immunologic heterogeneity

Miller

1982

Cancer Metast Rev

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“…Interactions affecting immune reactivity have also been reported. Mixtures of immunogenic and nonimmunogenic tumor cells can either induce or not induce overall immunity to tumor challenge, depending upon the relative proportions of the two types of cells (147). The immunogenicity of AKR leukemia cells is enhanced by immunization with mixtures of subpopulations that express different antigens (20).…”

Section: Tumor Cell Subpopulation Interactionsmentioning

confidence: 99%

Tumor heterogeneity: biological implications and therapeutic consequences

1983

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It is now appreciated that cancers can be composed of multiple clonal s~bpopulations of cancer cells which differ among themselves in many properties, including karyotype, growth rate, ability to metastasize, immunological characteristics, production and expression of markers, and sensitivity to therapeutic modalities. Such tumor heterogeneity has been demonstrated in a wide variety of animal tumors of differing etiology, tissue and cellular origin, and species. It has been shown in autochthonous, as well as transplanted, tumors. Similar results have been reported for human cancers, although much of the evidence that heterogeneity of human cancers, also reflects, at least in part, the existence of clonal subpopulations, is still indirect. Heterogeneity is not a unique property of malignancy. Preneoplastic tumors, as well as normal tissues, are also composed of cellular subpopulations.Proposed mechanisms for the origin of tumor heterogeneity include coalescence of multiple loci of cancer clones and the generation of diverse subpopulations from a single clone. This latter process could be due to genetic errors arising from classical genetic mechanisms or to the production of cellular variants as in normal tissue differentiation. Indeed, certain tumor subpopulations have been shown to produce variants at high frequency. In some cases this frequency can be modified by environmental circumstances. Nontumor cells may also contribute to production of cancer cell variants, perhaps, in the case of infiltrating phagocytic cells, by producing mutagens or by somatic hybridization with cancer cells. Production of tumor cell variants is a dynamic process which can occur at any time.Although tumors are mixed populations of cells, knowledge of the characteristics of individual components is not sufficient to predict the behavior of the whole. Individual cancer subpopulations can interact to affect each other's growth, immunogenicity, ability to metastasize, sensitivity to drugs, and clonal stability. The existence of multiple, interactive subpopulations provides a basis for the well-known phenomenon of 'tumor progression' in which tumors undergo qualitative changes in characteristics over the course of time. Selection of subpopulations better able to survive changing environmental circumstances allows for such changes as autonomy in regard to endogenous growth regulation, more "malignant' behavior, and loss of response to therapy. Tumor subpopulation interactions may play a regulatory role in this process.Tumor heterogeneity has obvious consequences to the design of effective therapy. It provides one rationale for combination therapies and suggests that initial treatment should be early and comprehensive. The continuing emergence of new clones suggests that treatment which is unsuccessful at one point might be effective later. Assays to predict effective therapy for individual patients need to address the multiplicity of tumor subpopulations and the ability of these subpopulations to influence each other. Subpopulation interacti...

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Escape of TA3 tumors from allogeneic immune rejection: theory and experiments

et al. 1974

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A factor promoting tumor growth in allogeneic mice was found in the ascites fluid of TA3-Ha tumor-bearing mice. Preliminary attempts t o isolate this factor resulted in a preparation (P3), devoid of free immunoglobulins or serum proteins, which had enhanced action in promoting tumor growth in vivo. Electron microscopy showed that the P3 preparation is of membranous origin. Biochemical assays for membrane marker enzymes were positive. 5'-Nucleotidase and alkaline a-glycerophosphatase activity was found. Chemical and gas-liquid chromatographic analysis of long-chain carboxylic acids present in the tumor cell membrane and in the P 3 revealed the presence of fatiy acids in almost identical ratios in both preparations, again indicating the membranous character of P3.The P3 preparation as well as the ascites fluid have immunogenic properties. They could induce immune tolerance if injected neonatally and the P3 preparation could immunize against the TA3-Ha tumor if injected intramuscularly or subcutaneously into adult mice. It had no effect if injected intravenous- A working hypothesis has been proposed according t o which TA3-Ha tumor cells produce highly reactive membranous decay products which intercept incoming immunocytes o r immunoglobulins before they can reach their targets o n living tumor cells. Whether this self protection of TA3 ascites tumors can be applied to other tumors remains t o be investigated.ly.

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Mixed Tumor Challenge of Strain Specific and Nonspecific TA3 Mouse Ascites Mammary Adenocarcinoma

Cited by 9 publications

References 3 publications

Intratumor immunologic heterogeneity

Intratumor immunologic heterogeneity

Tumor heterogeneity: biological implications and therapeutic consequences

Escape of TA3 tumors from allogeneic immune rejection: theory and experiments

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