Generation and decay of the immune response to a progressive fibrosarcoma. II. Failure to demonstrate postexcision immunity after the onset of T cell-mediated suppression of immunity.

Abstract

It was shown in the preceding companion paper (1) that early progressive growth of an immunogenic fibrosarcoma results in the acquisition by its syngeneic host of concomitant immunity to growth of a challenge implant, and of tumorsensitized Ly-l-2 + T cells that are capable of adoptively immunizing against an established tumor in y-irradiated recipients. It was shown, in addition, that after the tumor reaches a certain size, concomitant immunity and tumor-sensitized T cells are progressively lost, and that this is associated with the generation of Ly-1 +2-suppressor T cells capable, on passive transfer, of inhibiting the expression of adoptive immunity against an established tumor in T cell-deficient (TXB) 1 recipients. The evidence was interpreted as showing that progressive tumor growth evokes a mechanism of T cell-mediated concomitant immunity that is down-regulated by suppressor T cells before it develops sufficiently in magnitude to destroy the tumor. This knowledge that progressive tumor growth evokes a concomitant immune response that subsequently decays under the influence of suppressor T cells must surely be taken into account in assessing the results of the most commonly used test for tumor immunogenicity (2-4): determining whether surgical removal of a tumor results in immunity to growth of a subsequent implant of cells of that tumor. It might be expected, in this regard, that the immunological consequences of excising an immunogenic tumor would be determined by whether excision is performed during the generation of concomitant immunity or after it has decayed under the influence of suppressor T cells. It is apparent from the literature (5) that little is known about the relationship between the ability to demonstrate postexcision antitumor immunity and the state of concomitant immunity of the host at the time of excision. This paper will show that excising the meth A fibrosarcoma during the time that concomitant immunity is being generated results in the preservation of this immunity for a long period of time. In contrast, excising the tumor after T ceilmediated suppression of concomitant immunity does not result in the reemergence of immunity. Instead, the host remains unresponsive to the meth A tumor

Induction of Postsurgical Tumor Immunity and T-Cell Memory by a Poorly Immunogenic Tumor

“…This could be attributed to the fact that T reg cells return in a tumor-free environment. Studies published 20 years ago show that surgery before the growth of large highly immunogenic tumors prevents the generation of suppressor T cells (45), and more recent work has shown that surgery can reverse immune suppression in tumorbearing hosts (46,47). Indeed, B16 tumors have been shown to recruit T reg cells (48); however, further investigation will be required to determine if surgery prevents the induction of T reg cells that can suppress preprimed memory CD8 T-cell responses.…”

Prevalence of Regulatory T Cells Is Increased in Peripheral Blood and Tumor Microenvironment of Patients with Pancreas or Breast Adenocarcinoma

“…Experimental evidence suggests that down-regulation of immune response to cancer by concomitant development of suppressor cells may allow progressive local growth of tumors (25). When tumor cells are implanted in mice, an initial slow period of growth is followed by a rapid growth period with local invasion and metastatic spread.…”

OX40 Agonist Therapy Enhances CD8 Infiltration and Decreases Immune Suppression in the Tumor

“…The agonists were delivered early after tumor challenge, and the effects were lost if either CD4 or CD8 T cells were depleted during the priming or effector phases (20,46). The experiments described here occur at times beyond early tumor priming, such that the tumor-bearing animals may already have developed functional effector T cells, albeit within a suppressive environment (47,48). Thus, in these experiments, there was a lesser requirement for CD4 T cells in the response and more of a requirement to overcome CD8 tolerogenic mechanisms.…”