Improvement of cancer immunotherapy by combining molecular targeted therapy
In human cancer cells, a constitutive activation of MAPK, STAT3, β-catenin, and various other signaling pathways triggers multiple immunosuppressive cascades. These cascades result in the production of immunosuppressive molecules (e.g. TGF-β, IL-10, IL-6, VEGF, and CCL2) and induction of immunosuppr...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-05-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2013.00136/full |
| _version_ | 1819126884123803648 |
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| author | Yutaka eKawakami Tomonori eYaguchi Hidetoshi eSumimoto Chie eKudo-Saito Tomoko eIwata-Kajihara Shoko eNakamura Takahiro eTsujikawa Jeong Hoon Park Boryana K Popivanova Junichiro eMiyazaki Naoshi eKawamura |
| author_facet | Yutaka eKawakami Tomonori eYaguchi Hidetoshi eSumimoto Chie eKudo-Saito Tomoko eIwata-Kajihara Shoko eNakamura Takahiro eTsujikawa Jeong Hoon Park Boryana K Popivanova Junichiro eMiyazaki Naoshi eKawamura |
| author_sort | Yutaka eKawakami |
| collection | DOAJ |
| description | In human cancer cells, a constitutive activation of MAPK, STAT3, β-catenin, and various other signaling pathways triggers multiple immunosuppressive cascades. These cascades result in the production of immunosuppressive molecules (e.g. TGF-β, IL-10, IL-6, VEGF, and CCL2) and induction of immunosuppressive immune cells (e.g. regulatory T cells, tolerogenic dendritic cells, and myeloid derived suppressor cells). Consequently, immunosuppressive conditions are formed in tumor-associated microenvironments, including the tumor and sentinel lymph nodes. Some of these cancer-derived cytokines and chemokines impair immune cells and render them immunosuppressive via the activation of signaling molecules, such as STAT3, in the immune cells. Thus, administration of signal inhibitors may inhibit the multiple immunosuppressive cascades by acting simultaneously on both cancer and immune cells at the key regulatory points in the cancer-immune network. Since common signaling pathways are involved in manifestation of several hallmarks of cancer, including cancer cell proliferation/survival, invasion/metastasis, and immunosuppression, targeting these shared signaling pathways in combination with immunotherapy may be a promising strategy for cancer treatment. |
| first_indexed | 2024-12-22T08:03:07Z |
| format | Article |
| id | doaj.art-38bdc298949643cb85e8004c9e1b3b6c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-22T08:03:07Z |
| publishDate | 2013-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-38bdc298949643cb85e8004c9e1b3b6c2022-12-21T18:33:12ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2013-05-01310.3389/fonc.2013.0013649076Improvement of cancer immunotherapy by combining molecular targeted therapyYutaka eKawakami0Tomonori eYaguchi1Hidetoshi eSumimoto2Chie eKudo-Saito3Tomoko eIwata-Kajihara4Shoko eNakamura5Takahiro eTsujikawa6Jeong Hoon Park7Boryana K Popivanova8Junichiro eMiyazaki9Naoshi eKawamura10Keio University School of MedicineKeio University School of MedicineKeio University School of MedicineKeio University School of MedicineKeio University School of MedicineKeio University School of MedicineKeio University School of MedicineKeio University School of MedicineKeio University School of MedicineKeio University School of MedicineKeio University School of MedicineIn human cancer cells, a constitutive activation of MAPK, STAT3, β-catenin, and various other signaling pathways triggers multiple immunosuppressive cascades. These cascades result in the production of immunosuppressive molecules (e.g. TGF-β, IL-10, IL-6, VEGF, and CCL2) and induction of immunosuppressive immune cells (e.g. regulatory T cells, tolerogenic dendritic cells, and myeloid derived suppressor cells). Consequently, immunosuppressive conditions are formed in tumor-associated microenvironments, including the tumor and sentinel lymph nodes. Some of these cancer-derived cytokines and chemokines impair immune cells and render them immunosuppressive via the activation of signaling molecules, such as STAT3, in the immune cells. Thus, administration of signal inhibitors may inhibit the multiple immunosuppressive cascades by acting simultaneously on both cancer and immune cells at the key regulatory points in the cancer-immune network. Since common signaling pathways are involved in manifestation of several hallmarks of cancer, including cancer cell proliferation/survival, invasion/metastasis, and immunosuppression, targeting these shared signaling pathways in combination with immunotherapy may be a promising strategy for cancer treatment.http://journal.frontiersin.org/Journal/10.3389/fonc.2013.00136/fullImmunosuppressionImmunotherapyTumor MicroenvironmentNF-κBMAPKstat3 |
| spellingShingle | Yutaka eKawakami Tomonori eYaguchi Hidetoshi eSumimoto Chie eKudo-Saito Tomoko eIwata-Kajihara Shoko eNakamura Takahiro eTsujikawa Jeong Hoon Park Boryana K Popivanova Junichiro eMiyazaki Naoshi eKawamura Improvement of cancer immunotherapy by combining molecular targeted therapy Frontiers in Oncology Immunosuppression Immunotherapy Tumor Microenvironment NF-κB MAPK stat3 |
| title | Improvement of cancer immunotherapy by combining molecular targeted therapy |
| title_full | Improvement of cancer immunotherapy by combining molecular targeted therapy |
| title_fullStr | Improvement of cancer immunotherapy by combining molecular targeted therapy |
| title_full_unstemmed | Improvement of cancer immunotherapy by combining molecular targeted therapy |
| title_short | Improvement of cancer immunotherapy by combining molecular targeted therapy |
| title_sort | improvement of cancer immunotherapy by combining molecular targeted therapy |
| topic | Immunosuppression Immunotherapy Tumor Microenvironment NF-κB MAPK stat3 |
| url | http://journal.frontiersin.org/Journal/10.3389/fonc.2013.00136/full |
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