Search

Interactions of cancer cells with components of their microenvironment are crucial determinants in the decision making process which determines whether the cancer cells will progress towards a highly malignant phenotype or whether they will stay dormant or disappear altogether. The tumor microenvironment is composed of a plethora of soluble and cellular components. Many of these components deliver signals to tumor cells and thus modulate their phenotype thereby driving tumor progression. This chapter focuses on the interaction of tumor cells with endothelial cells through endothelial selectins and their fucosylated ligands expressed by the tumor cells. Comparisons are drawn between the utilization of this interaction axis by inflammatory leukocytes and by tumor cells.

There is ample evidence that alterations in oncogenes and tumor suppressor genes are causally involved in malignant transformation (1-3). In addition to alterations in these class I cancer genes (4), changes in the expression of numerous genes whose DNA was not altered i.e. class II cancer genes (4), play crucial roles in tumorigenesis and in tumor progression. Among the important class II cancer genes are proteases, angiogenic factors and angiogenesis inhibitors, cytokines and chemokines and their receptors as well as various adhesion molecules (5-8). It seems that class II cancer genes play a more significant role in the process of tumor progression than in cellular transformation and primary tumorigenesis (4).

The NK activity of BALB/c mice bearing carcinomas induced by intragastric administration of dimethylbenzanthracene (DMBA) is severely depressed. The aim of the present study was to determine when, in relation to tumor appearance or to DMBA administration, was this depression first demonstrable.

In situ humoral immunity as an indispensable component of host-tumor relationship is being studied in our laboratory using various tumor systems (1–3). It is now well established that immunoglobulins localize in vivo within the tumor tissue of man and animals (3). Some of these tumor-associated Ig molecules may be anti tumor antibodies induced in tumor-bearers (e. g.2,4).

Masking of cell surface antigens was first suggested as one of the mechanisms by which enhancing antibodies operate in a tumor bearing host (1). Such a masking, inferred also from studies showing that in vivo growing tumor cells are coated with immunoglobulin (Ig), is lately considered a key event in many alternative pathways by which the tumor escapes the immune reactivity of the host (2). This consideration is supported by the following indirect evidence: 1. Enhancement of tumor growth by immunoglobulin (Ig)-containing tumor eluates (3–4). 2. Blocking of in vitro cell mediated antitumor activity by tumor eluates, of human and animal origin (4–6). 3. Demonstration of an increased ability of human tumor cells to stimulate DNA synthesis in autochthonous lymphocytes following “unmasking” of tumor antigens (7). The association between tumor cell surface and Ig has been demonstrated directly (8). Yet it is not clear whether the coating of tumor cells by Ig and the masking of cell surface antigens is the very same phenomenon. This study was aimed to determine whether part of the Ig coating of Polyoma virus induced mouse tumor cells (SEYF-a, 9) consists of specific antibodies.

Tumor cells, whether of lymphoid or non-lymphoid origin, are coated in vivo with a surface layer of immunoglobulin (Ig) (1). At least some of this surface Ig may represent anti tumor antibody (1,2) that is most likely attached to the surface through the Fab portion of the molecule. However, there have been reports that some non-lymphoid tumors contain cells which bear an Fc or Fc-like receptor (3–5,11). The Ig-coat of these Fc-reactive cells could contain anti tumor antibodies, as well as non-tumor antibodies, attached to the surface through the Fc part of the molecule (most likely as immune complex). In this paper we present evidence that non-lymphoid tumor populations can fix both in vivo and in vitro tumor unrelated antibodies or immune complexes.

Because of several valid (and some invalid) reasons, the research field of tumor immunology has been declining in popularity. The Simplistic dogmas, articles of faith, and theories of the late 1960s and early 1970s on the immuno logical mechanisms of the host-tumor interrelationships have frequently been refuted by some of the new developments in cancer biology, cancer biochem istry, and immunology. Furthermore, some of the conventional assays used to monitor "tumor-host immune relations" did not always reflect the host's true clinical situation or his prognosis. Several approaches to immunological interven tion were less successful than expected. In addition, the concept of "immune surveillance," which was basic to many researchers in the field of cancer im munology, seemed to fall apart. Much of the criticism was based on results from solid, well-performed, and well-controlled experiments, but there was also un just criticism based on ill-conceived and badly performed studies, and on misin terpretations of experimental data. There are many misconceptions about the tumor-host relationship. It is very often assumed that tumor immunity, as expressed systemically, is truly reflected at the tumor site. Several studies reported in this volume and elsewhere indicate that such is not always the case. Certain immune effectors may be selectively prevented from reaching the tumor site or the close vicinity of the tumor cells because of mechanical or chemical barriers, whereas others may be selectively attracted to the site by chemotaxis or other mechanisms."

Isolation of cellular and humoral immune components from solid neoplasms is a relatively new approach to the study of a host’s response to its tumor. While this line of research has the potential for providing a great deal of new information about antitumor immunity, as might be expected it is an approach that is fraught with technical problems. The objectives of this chapter are to call attention to these problems and, when possible, to suggest solutions to them. By including such information in this monograph it is hoped that new investigators in the field will be provided with a starting point from which to launch their research that is technically more sound than would otherwise have been the case. Emphasis has been given to the recovery of inflammatory cells from tumors, in view of the comprehensive review of intratumoral immunoglobulin recently published by Witz (1977).

The principal conclusion emerging from the numerous studies dealing with parameters of host-tumor relations is that the tumor-bearing host is capable of mounting an immune response against the tumor. (For reviews see Hellstrom and Hellstrom, 1969, 1970a; Gold, 1971 a, b; Klein, 1971; Morton et al., 1971; Nishioka, 1971.) The response which is elicited both at the cellular and at the humoral levels occurs in natural circumstances (human cancer patients; laboratory animals bearing spontaneous tumors) as well as under experimental conditions (laboratory animals bearing virus or carcinogen-induced neoplasms).

Injections of tumor extracts to mice which were subsequently immunized with sheep erythrocytes, cause a decreased plaque and rosette formation by the spleen cells of the injected mice. There is no indication that extracts from non malignant tissues have a similar activity. The suppressive effect was obtained only when the tumor extract was administered prior to antigen. The tumor extract was not toxic in-vitro to plaque forming cells.