Lymph node tumor metastases: more susceptible than primary tumors to CD8+ T-cell immune destruction

Contassot, Emmanuel; Preynat‐Seauve, Olivier; French, Lars E.; Huard, Bertrand

doi:10.1016/j.it.2009.08.001

Cited by 11 publications

(4 citation statements)

References 38 publications

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“…This results in the expansion of T cell clones in the affected lymph nodes. This direct priming does not occur in unaffected lymph nodes, as is the case in early-stage disease (Contassot et al, 2009). The results of Yamamoto et al expand the earlier findings of Garzetti et al (1995), who did not find any clinical significance in the lymphocyte distribution in lymph nodes in patients with early-stage disease.…”

Section: Adaptive Immune Cellssupporting

confidence: 69%

The immune system in the normal endometrium and implications for endometrial cancer development

Vanderstraeten

Tuyaerts

Amant

2015

Journal of Reproductive Immunology

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Although described for the first time some decades ago, the contribution of the immune system to the establishment of tumors has not been extensively pursued for a long time. Over the last decade, however, more and more evidence has been accumulating concerning the role the immune system plays in tumor development and progression and its possible role in patient prognosis. In addition, interest is growing in preclinical and clinical research concerning the use of the immune system in the treatment of cancer. Immunotherapy for gynecological cancers in general, and for endometrial cancer in particular, is still in its infancy. Only a small number of studies, with varying success rates, have been published. Here, we provide a concise overview of the literature available on the role of the immune system in the normal endometrium and in endometrial cancer, in addition to the possible implications for future immunotherapeutic studies.

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Section: Adaptive Immune Cellssupporting

confidence: 69%

The immune system in the normal endometrium and implications for endometrial cancer development

Vanderstraeten

Tuyaerts

Amant

2015

Journal of Reproductive Immunology

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“…The unique ability of histotripsy to markedly upregulate circulating numbers of CD8+ T cells specific for the minor tumor antigen GP33 suggests that histotripsy may facilitate cross-presentation of tumor antigens. [37][38][39] Indeed, the induction of inflammatory and antigen-presenting cell populations within the ablated tumor and the therapeutically favorable skewing of tumorspecific CD8+ effector:CD4+ regulatory T cells within the systemic circulation suggest that the local immunostimulatory effects of histotripsy may be potent enough to globally reorient the systemic immune system toward tumor antigen recognition. Radiation therapy has been proposed as a means to promote apoptotic immunogenic cell death.…”

Section: Discussionmentioning

confidence: 99%

Non-thermal histotripsy tumor ablation promotes abscopal immune responses that enhance cancer immunotherapy

Worlikar

Felsted

et al. 2020

J Immunother Cancer

135

168

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BackgroundDeveloping the ability to use tumor-directed therapies to trigger potentially therapeutic immune responses against cancer antigens remains a high priority for cancer immunotherapy. We hypothesized that histotripsy, a novel non-invasive, non-thermal ablation modality that uses ultrasound-generated acoustic cavitation to disrupt tissues, could engender adaptive immune responses to tumor antigens.MethodsImmunocompetent C57BL/6 mice inoculated with flank melanoma or hepatocellular carcinoma tumors were treated with histotripsy, thermal ablation, radiation therapy, or cytotoxic T lymphocyte-associated protein-4 (CTLA-4) blockade checkpoint inhibition. Lymphocyte responses were measured using flow cytometric and immunohistochemical analyses. The impact of histotripsy on abscopal immune responses was assessed in mice bearing bilateral tumors, or unilateral tumors with pulmonary tumors established via tail vein injection.ResultsHistotripsy ablation of subcutaneous murine melanoma tumors stimulated potent local intratumoral infiltration of innate and adaptive immune cell populations. The magnitude of this immunostimulation was stronger than that seen with tumor irradiation or thermal ablation. Histotripsy also promoted abscopal immune responses at untreated tumor sites and inhibited growth of pulmonary metastases. Histotripsy was capable of releasing tumor antigens with retained immunogenicity, and this immunostimulatory effect was associated with calreticulin translocation to the cellular membrane and local and systemic release of high mobility group box protein 1. Histotripsy ablation potentiated the efficacy of checkpoint inhibition immunotherapy in murine models of melanoma and hepatocellular carcinoma.ConclusionsThese preclinical observations suggest that non-invasive histotripsy ablation can be used to stimulate tumor-specific immune responses capable of magnifying the impact of checkpoint inhibition immunotherapy.

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“…For one, they appear to have a more immunosuppressive cytokine environment (6,9), even though they are tumor antigen-experienced and can mount strong antitumor CTL responses when activated, for example, with a vaccine against a tumor-specific antigen (10,11). Second, they are lymphangiogenic, and lymph node lymphangiogenesis has been shown to precede metastasis (1,2).…”

Section: Lymphatic Vessels and Cancer Progressionmentioning

confidence: 99%

Immunomodulatory Roles of Lymphatic Vessels in Cancer Progression

Swartz

2014

Cancer Immunology Research

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Lymphatic vessels in the tumor microenvironment are known to foster tumor metastasis in many cancers, and they can undergo activation, hyperplasia, and lymphangiogenesis in the tumor microenvironment and in the tumor-draining lymph node. The mechanism underlying this correlation was originally considered as lymphatic vessels providing a physical route for tumor cell dissemination, but recent studies have highlighted new roles of the lymphatic endothelium in regulating host immunity. These include indirectly suppressing T-cell function by secreting immunosuppressive factors and inhibiting dendritic cell (DC) maturation, as well as directly driving Tcell tolerance by antigen presentation in the presence of inhibitory ligands.

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Lymph node tumor metastases: more susceptible than primary tumors to CD8+ T-cell immune destruction

Cited by 11 publications

References 38 publications

The immune system in the normal endometrium and implications for endometrial cancer development

The immune system in the normal endometrium and implications for endometrial cancer development

Non-thermal histotripsy tumor ablation promotes abscopal immune responses that enhance cancer immunotherapy

Immunomodulatory Roles of Lymphatic Vessels in Cancer Progression

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