A serum-mediated mechanism for concomitant resistance shared by immunogenic and non-immunogenic murine tumours

Franco, M; Bustuoabad, Oscar D.; Gianni, Pedro di; Goldman, Allan L.; Pasqualini, Christiane Dosne; Ruggiero, Raúl A.

doi:10.1038/bjc.1996.335

Cited by 30 publications

(56 citation statements)

References 20 publications

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“…2A). Furthermore, the groups were inoculated with a secondary tumor implant to evaluate the CI, which evaluates the capacity of T cells to reject a secondary implant (18). The two groups showed the same proportion of tumor rejection (75%), suggesting that B cell depletion did not prevent the early activation stage that occurs in the TDLN following tumor implant.…”

Section: Systemic B Cell Depletion Exerts Opposite Effects During Tummentioning

confidence: 99%

“…Immunological characteristics of MCC and its rapid growth in vivo make it a suitable model to study mechanisms underlying tumor immunity and tumor-induced immunosuppression. Using this model, previous studies have demonstrated that small tumor-bearing mice (TBM) are able to reject a secondary distant implant of the same tumor through a T cell mediated-reaction, phenomenon known as concomitant immunity (CI) (18). Later, in the tolerogenic stage, CI is no longer detected and a second tumor implant grows without being rejected (18).…”

Section: Introductionmentioning

confidence: 99%

“…Methylcolanthrene-induced murine fibrosarcoma (MCC) is a highly immunogenic tumor that elicits an early specific antitumor immune reaction, which is not strong enough to impede tumor growth (18)(19)(20)(21). The antitumor response declines at a certain tumor volume (~500 mm 3 ) and disappears comprising a state of tolerance (18)(19)(20)(21). Immunological characteristics of MCC and its rapid growth in vivo make it a suitable model to study mechanisms underlying tumor immunity and tumor-induced immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

“…Using this model, previous studies have demonstrated that small tumor-bearing mice (TBM) are able to reject a secondary distant implant of the same tumor through a T cell mediated-reaction, phenomenon known as concomitant immunity (CI) (18). Later, in the tolerogenic stage, CI is no longer detected and a second tumor implant grows without being rejected (18). MCC growth was also found to induce a series of alterations in the cell composition of tumor-draining lymph nodes (TDLN), including the progressive increase in B cells with the emergence of an IL-10-producing subpopulation (20,22).…”

Section: Introductionmentioning

confidence: 99%

“…Evidence that accounts for the role of B cells in tumor-induced immunosuppression includes the existence of human B cells with a regulatory phenotype in solid tumors (11), the B cell-mediated induction of Tregs expansion (12)(13)(14) and the increase of tumor growth (12,(15)(16)(17). Methylcolanthrene-induced murine fibrosarcoma (MCC) is a highly immunogenic tumor that elicits an early specific antitumor immune reaction, which is not strong enough to impede tumor growth (18)(19)(20)(21). The antitumor response declines at a certain tumor volume (~500 mm 3 ) and disappears comprising a state of tolerance (18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

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B cells inhibit the antitumor immunity against an established murine fibrosarcoma

et al. 2017

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Abstract. Despite the classic role of B cells in favoring the immune response, an inhibitory action of B lymphocytes in tumor immunity has emerged in certain studies. In methylcolanthrene-induced murine fibrosarcoma (MCC), the loss of immunogenicity and the establishment of tolerance are paralleled by systemic immune suppression and the appearance of B + IL-10 + cells in tumor-draining lymph nodes. The present study aimed to assess the role of the B + IL-10 + cell population in the immune evasion and tolerance induced by MCC through the depletion of B cells in mice at various times of tumor progression: Prior to or subsequent to tumor implantation. Tumor growth and immunological parameters were evaluated. B cell depletion prior to tumor inoculum enhanced tumor growth, initiating the onset of the tumor-induced systemic immune response; however, an increase in the T regulatory cells (Tregs) at the tumor-draining lymph node could account for tumor exacerbation. B cell depletion once the tumor was established resulted in decreased tumor growth and a delayed onset of tolerance. Additionally, B cell absence exacerbated T cell dependent-tumor rejection, reduced Tregs and increased cytotoxic CD8 + T cells. In vitro analysis showed a direct effect of B cells upon T cell proliferation.In conclusion, B cell depletion exerts opposite effects when performed prior to or subsequent to tumor implantation. In this initially immunogenic tumor, B cell absence would delay the establishment of immunological tolerance probably by unmasking a pre-existing antitumor response. The present findings elucidate the convenience of modulating B cells in the development of future and more effective immunotherapies against cancer. IntroductionThe role of the host immune system in the control of cancer progression has been assessed for several years; at present, it is vastly accepted that antitumor immunity occurs and that numerous tumors have developed mechanisms to escape immune control, leading to malignant progression (1). The mechanisms responsible for antitumor immunity failure in individuals with cancer include a wide diversity of soluble immunosuppressive factors, including transforming growth factor β (TGFβ), interleukin 10 (IL-10), reactive oxygen species (ROS), enzymes and inhibitory ligands such as Fas ligand (FasL) or TNF-related apoptosis-inducing ligand, released by tumor cells or by other regulatory cells in the tumor microenvironment (2). The majority of immunotherapies against cancer aim to counteract the action of regulatory cells in order to achieve tumor remission or prevent recurrences; of these, T regulatory cells (Tregs) have been the major focus of efforts to therapeutically modulate their inhibitory activity (3,4

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Section: Systemic B Cell Depletion Exerts Opposite Effects During Tummentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

B cells inhibit the antitumor immunity against an established murine fibrosarcoma

et al. 2017

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Primary melanoma tumor inhibits metastasis through alterations in systemic hemostasis

et al. 2016

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Progression from a primary tumor to distant metastases requires extensive interactions between tumor cells and their microenvironment. The primary tumor is not only the source of metastatic cells but also can also modulate host responses to these cells, leading to an enhancement or inhibition of metastasis. Tumor-mediated stimulation of bone marrow can result in pre-metastatic niche formation and increased metastasis. However, a primary tumor can also inhibit metastasis through concomitant tumor resistance-inhibition of metastatic growth by existing tumor mass. Here, we report that the presence of a B16F10 primary tumor significantly restricted numbers and sizes of experimental lung metastases through reduction of circulating platelets and reduced formation of metastatic tumor cell-associated thrombi. Tumor-bearing mice displayed splenomegaly, correlated with primary tumor size and platelet count. Reduction in platelet numbers in tumor-bearing animals was responsible for metastatic inhibition, as restoration of platelet numbers using isolated platelets re-established both tumor cell-associated thrombus formation and experimental metastasis. Consumption of platelets due to a B16F10 primary tumor is a form of concomitant tumor resistance and demonstrates the systemic impact of a growing tumor. Understanding the interplay between primary tumors and metastases is essential, as clarification of concomitant tumor resistance mechanisms may allow inhibition of metastatic growth following tumor resection. Key messages Mice with a primary B16F10 tumor had reduced metastasis vs. mice without a primary tumor. Tumor-bearing mice had splenomegaly and fewer platelets and tumor-associated thrombi. Restoring platelets restored tumor-associated thrombi and increased metastasis. This work shows the impact that a primary tumor can have on systemic metastasis. Understanding these interactions may lead to improved ways to inhibit metastasis.

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Small numbers of residual tumor cells at the site of primary inoculation are critical for anti-tumor immunity following challenge at a secondary location

Kakinuma

Nadiminti

Lonsdorf

et al. 2006

Cancer Immunol Immunother

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Luciferase-transduced B16 murine melanoma cells (luc-B16) inoculated in ear skin do not form tumors but prevent tumor formation by luc-B16 cells injected into the footpad. To determine the requirements for such immunity, we followed the fate of luc-B16 cells following ear injection. Surprisingly, small numbers of viable luc-B16 cells were detected in tumor-free mouse skin for up to 60 days post-inoculation. After 1 week, the number of Foxp3(+)CD4(+)CD25(+) T cells (along with foxp3 mRNA expression) increased rapidly in the injected ear skin. Residual tumor cells in ears were reduced in mice treated with anti-CD25 mAb and in CD4-deficient mice, but increased in CD8-deficient mice. Strikingly, the loss of luc-B16 cells in the ear skin, either spontaneously or following amputation of the injected ear, resulted in significantly enhanced tumor formation by parental and luciferase-expressing B16 cells after footpad injection. These studies suggest that small numbers of tumor cells (possibly regulated by CD4(+)CD25(+) regulatory T cells expressing Foxp3) are required for effective host anti-tumor responses at alternate inoculation sites.

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A serum-mediated mechanism for concomitant resistance shared by immunogenic and non-immunogenic murine tumours

Cited by 30 publications

References 20 publications

B cells inhibit the antitumor immunity against an established murine fibrosarcoma

B cells inhibit the antitumor immunity against an established murine fibrosarcoma

Primary melanoma tumor inhibits metastasis through alterations in systemic hemostasis

Small numbers of residual tumor cells at the site of primary inoculation are critical for anti-tumor immunity following challenge at a secondary location

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