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Lymphatic dysfunction attenuates tumor immunity through impaired antigen presentation

Identifieur interne : 001B74 ( Main/Merge ); précédent : 001B73; suivant : 001B75

Lymphatic dysfunction attenuates tumor immunity through impaired antigen presentation

Auteurs : Takayuki Kimura [Japon] ; Makoto Sugaya [Japon] ; Tomonori Oka [Japon] ; Andrew Blauvelt [États-Unis] ; Hitoshi Okochi [Japon] ; Shinichi Sato [Japon]

Source :

RBID : PMC:4627236

Descripteurs français

English descriptors

Abstract

Tumor growth and metastasis of cancer involve autonomous tumor cell growth and host-tumor interactions. While tumor-specific immunity has been intensively studied in vitro, dynamic roles of lymphatic transport on tumor immunity in vivo have not been fully elucidated. In this study, we examined tumor growth and anti-tumor immune responses using kCYC mice, which demonstrate severe lymphatic dysfunction. Primary tumor growth was augmented in kCYC mice (compared to wild-type mice) when B16 melanoma or EL-4 lymphoma cells were subcutaneously injected. Expression of inflammatory cytokines such as IFN-γ, TNF-α, and IL-2 as well as IL-10 expression in draining lymph nodes (LNs) was significantly reduced in kCYC mice after tumor inoculation. Moreover, decreased levels of tumor-associated antigens were detected in draining LNs in kCYC mice, together with impaired antigen presentation. CD8+ T cells in draining LNs derived from kCYC mice bearing B16 melanoma also showed significantly decreased cytotoxic activity in vitro. Finally, tumor suppression activity of CD8+ T cells derived from kCYC mice bearing B16 melanoma was reduced when adoptively transferred to naive wild-type mice. In summary, these findings suggest that lymphatic transport is essential in generating optimal tumor-specific immune responses mediated by CD8+ T cells.


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PubMed: 26098776
PubMed Central: 4627236

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PMC:4627236

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<country xml:lang="fr">Japon</country>
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<name sortKey="Sato, Shinichi" sort="Sato, Shinichi" uniqKey="Sato S" first="Shinichi" last="Sato">Shinichi Sato</name>
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<title level="j">Oncotarget</title>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Adoptive Transfer</term>
<term>Animals</term>
<term>Antigen Presentation</term>
<term>Antigens, Neoplasm (immunology)</term>
<term>Antigens, Neoplasm (metabolism)</term>
<term>CD8-Positive T-Lymphocytes (immunology)</term>
<term>CD8-Positive T-Lymphocytes (metabolism)</term>
<term>CD8-Positive T-Lymphocytes (transplantation)</term>
<term>Cyclins (genetics)</term>
<term>Cyclins (metabolism)</term>
<term>Cytokines (immunology)</term>
<term>Cytokines (metabolism)</term>
<term>Inflammation Mediators (immunology)</term>
<term>Inflammation Mediators (metabolism)</term>
<term>Lymph Nodes (immunology)</term>
<term>Lymph Nodes (metabolism)</term>
<term>Lymph Nodes (pathology)</term>
<term>Lymphoma (genetics)</term>
<term>Lymphoma (immunology)</term>
<term>Lymphoma (metabolism)</term>
<term>Lymphoma (pathology)</term>
<term>Melanoma, Experimental (genetics)</term>
<term>Melanoma, Experimental (immunology)</term>
<term>Melanoma, Experimental (metabolism)</term>
<term>Melanoma, Experimental (pathology)</term>
<term>Mice, Transgenic</term>
<term>Skin Neoplasms (genetics)</term>
<term>Skin Neoplasms (immunology)</term>
<term>Skin Neoplasms (metabolism)</term>
<term>Skin Neoplasms (pathology)</term>
<term>Time Factors</term>
<term>Tumor Burden</term>
<term>Tumor Escape</term>
<term>Viral Proteins (genetics)</term>
<term>Viral Proteins (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Animaux</term>
<term>Antigènes néoplasiques (immunologie)</term>
<term>Antigènes néoplasiques (métabolisme)</term>
<term>Charge tumorale</term>
<term>Cyclines (génétique)</term>
<term>Cyclines (métabolisme)</term>
<term>Cytokines (immunologie)</term>
<term>Cytokines (métabolisme)</term>
<term>Facteurs temps</term>
<term>Lymphocytes T CD8+ (immunologie)</term>
<term>Lymphocytes T CD8+ (métabolisme)</term>
<term>Lymphocytes T CD8+ (transplantation)</term>
<term>Lymphomes (anatomopathologie)</term>
<term>Lymphomes (génétique)</term>
<term>Lymphomes (immunologie)</term>
<term>Lymphomes (métabolisme)</term>
<term>Médiateurs de l'inflammation (immunologie)</term>
<term>Médiateurs de l'inflammation (métabolisme)</term>
<term>Mélanome expérimental (anatomopathologie)</term>
<term>Mélanome expérimental (génétique)</term>
<term>Mélanome expérimental (immunologie)</term>
<term>Mélanome expérimental (métabolisme)</term>
<term>Noeuds lymphatiques (anatomopathologie)</term>
<term>Noeuds lymphatiques (immunologie)</term>
<term>Noeuds lymphatiques (métabolisme)</term>
<term>Protéines virales (génétique)</term>
<term>Protéines virales (métabolisme)</term>
<term>Présentation d'antigène</term>
<term>Souris transgéniques</term>
<term>Transfert adoptif</term>
<term>Tumeurs cutanées (anatomopathologie)</term>
<term>Tumeurs cutanées (génétique)</term>
<term>Tumeurs cutanées (immunologie)</term>
<term>Tumeurs cutanées (métabolisme)</term>
<term>Échappement de la tumeur à la surveillance immunitaire</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Cyclins</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Antigens, Neoplasm</term>
<term>Cytokines</term>
<term>Inflammation Mediators</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Antigens, Neoplasm</term>
<term>Cyclins</term>
<term>Cytokines</term>
<term>Inflammation Mediators</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr">
<term>Lymphomes</term>
<term>Mélanome expérimental</term>
<term>Noeuds lymphatiques</term>
<term>Tumeurs cutanées</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Lymphoma</term>
<term>Melanoma, Experimental</term>
<term>Skin Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Cyclines</term>
<term>Lymphomes</term>
<term>Mélanome expérimental</term>
<term>Protéines virales</term>
<term>Tumeurs cutanées</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Antigènes néoplasiques</term>
<term>Cytokines</term>
<term>Lymphocytes T CD8+</term>
<term>Lymphomes</term>
<term>Médiateurs de l'inflammation</term>
<term>Mélanome expérimental</term>
<term>Noeuds lymphatiques</term>
<term>Tumeurs cutanées</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>CD8-Positive T-Lymphocytes</term>
<term>Lymph Nodes</term>
<term>Lymphoma</term>
<term>Melanoma, Experimental</term>
<term>Skin Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>CD8-Positive T-Lymphocytes</term>
<term>Lymph Nodes</term>
<term>Lymphoma</term>
<term>Melanoma, Experimental</term>
<term>Skin Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Antigènes néoplasiques</term>
<term>Cyclines</term>
<term>Cytokines</term>
<term>Lymphocytes T CD8+</term>
<term>Lymphomes</term>
<term>Médiateurs de l'inflammation</term>
<term>Mélanome expérimental</term>
<term>Noeuds lymphatiques</term>
<term>Protéines virales</term>
<term>Tumeurs cutanées</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Lymph Nodes</term>
<term>Lymphoma</term>
<term>Melanoma, Experimental</term>
<term>Skin Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="transplantation" xml:lang="en">
<term>CD8-Positive T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Adoptive Transfer</term>
<term>Animals</term>
<term>Antigen Presentation</term>
<term>Mice, Transgenic</term>
<term>Time Factors</term>
<term>Tumor Burden</term>
<term>Tumor Escape</term>
</keywords>
<keywords scheme="MESH" qualifier="transplantation" xml:lang="fr">
<term>Animaux</term>
<term>Charge tumorale</term>
<term>Facteurs temps</term>
<term>Lymphocytes T CD8+</term>
<term>Présentation d'antigène</term>
<term>Souris transgéniques</term>
<term>Transfert adoptif</term>
<term>Échappement de la tumeur à la surveillance immunitaire</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Tumor growth and metastasis of cancer involve autonomous tumor cell growth and host-tumor interactions. While tumor-specific immunity has been intensively studied
<italic>in vitro</italic>
, dynamic roles of lymphatic transport on tumor immunity
<italic>in vivo</italic>
have not been fully elucidated. In this study, we examined tumor growth and anti-tumor immune responses using
<italic>kCYC</italic>
mice, which demonstrate severe lymphatic dysfunction. Primary tumor growth was augmented in
<italic>kCYC</italic>
mice (compared to wild-type mice) when B16 melanoma or EL-4 lymphoma cells were subcutaneously injected. Expression of inflammatory cytokines such as IFN-γ, TNF-α, and IL-2 as well as IL-10 expression in draining lymph nodes (LNs) was significantly reduced in
<italic>kCYC</italic>
mice after tumor inoculation. Moreover, decreased levels of tumor-associated antigens were detected in draining LNs in
<italic>kCYC</italic>
mice, together with impaired antigen presentation. CD8
<sup>+</sup>
T cells in draining LNs derived from
<italic>kCYC</italic>
mice bearing B16 melanoma also showed significantly decreased cytotoxic activity
<italic>in vitro</italic>
. Finally, tumor suppression activity of CD8
<sup>+</sup>
T cells derived from
<italic>kCYC</italic>
mice bearing B16 melanoma was reduced when adoptively transferred to naive wild-type mice. In summary, these findings suggest that lymphatic transport is essential in generating optimal tumor-specific immune responses mediated by CD8
<sup>+</sup>
T cells.</p>
</div>
</front>
<back>
<div1 type="bibliography">
<listBibl>
<biblStruct>
<analytic>
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<name sortKey="Payne, As" uniqKey="Payne A">AS Payne</name>
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</author>
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