Radiation Enhances the Efficacy of Antitumor Immunotherapy with an Immunocomplex of Interleukin-2 and its Monoclonal Antibody

Takahashi, Yutaka; Yasui, Toshimichi; Minami, Kazumasa; Tamari, Keisuke; Otani, Keisuke; Seo, Yuji; Isohashi, Fumiaki; Koike, Masahiko; Ogawa, Kazuhiko

doi:10.21873/anticanres.12140

Cited by 6 publications

(4 citation statements)

References 34 publications

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“…However, anti-PD-1 and AMD3100 co-administration synergistically expands infiltrating CTLs, enhances tumor growth control and prolongs survival 80 . Similarly to CXCR4 antagonist, a variety of iSV agents have reported synergistic effects in the context of NK and T cell based ACT 81 - 85 , DC vaccination 86 , 87 and chemotherapy 88 or radiotherapy 89 . Regarding cancer vaccines, CTLA-4 blockade was found to cooperate with cryotreated tumor lysate-pulsed DC vaccine in a primary tumor control to prevent the outgrowth of lung metastasis by reducing levels of Tregs and increasing infiltration of cytotoxic CD8 + lymphocytes inside the metastatic tumor 90 .…”

Section: Lessons From Preclinical Studiesmentioning

confidence: 99%

Immunotherapy in soft tissue and bone sarcoma: unraveling the barriers to effectiveness

Panagi¹,

Pilavaki²,

Constantinidou³

et al. 2022

Theranostics

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Sarcomas are uncommon malignancies of mesenchymal origin that can arise throughout the human lifespan, at any part of the body. Surgery remains the optimal treatment modality whilst response to conventional treatments, such as chemotherapy and radiation, is minimal. Immunotherapy has emerged as a novel approach to treat different cancer types but efficacy in soft tissue sarcoma and bone sarcoma is limited to distinct subtypes. Growing evidence shows that cancer-stroma cell interactions and their microenvironment play a key role in the effectiveness of immunotherapy. However, the pathophysiological and immunological properties of the sarcoma tumor microenvironment in relation to immunotherapy advances, has not been broadly reviewed. Here, we provide an up-to-date overview of the different immunotherapy modalities as potential treatments for sarcoma, identify barriers posed by the sarcoma microenvironment to immunotherapy, highlight their relevance for impeding effectiveness, and suggest mechanisms to overcome these barriers.

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Section: Lessons From Preclinical Studiesmentioning

confidence: 99%

Immunotherapy in soft tissue and bone sarcoma: unraveling the barriers to effectiveness

Panagi¹,

Pilavaki²,

Constantinidou³

et al. 2022

Theranostics

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“…Normally, MHC-I presents intracellular antigens, such as the ones derived from self-proteins and viral proteins, to CD8 + T lymphocytes while extracellular antigens are generally presented to CD4 + T lymphocytes by MHC-II (reviewed in 54). Effective tumor antigen presentation and the consequent effector T lymphocyte responses and access to the TME are essential for clinical responses to immunotherapy (55) and are associated with positive clinical outcomes (56). Reduction in MHC expression and expression of non-classical molecules is frequently observed in different types of cancers, leading to compromised antigen presentation and/or immune evasion (reviewed in 52), which can influence tumor progression and resistance to immunotherapy (57).…”

Section: The Dual Role Of Autophagy In Antigen Presentationmentioning

confidence: 99%

“…On the other hand, autophagy activation on tumor cells may promote a reduction in MHC-I and an increase in PD-1 and CTLA-4 expression, leading to tumor progression. Sources(11,28,34,47,49,(51)(52)(53)(54)(55)(56).…”

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confidence: 99%

The Role of Autophagy in Tumor Immunology—Complex Mechanisms That May Be Explored Therapeutically

et al. 2020

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The tumor microenvironment (TME) is complex, and its composition and dynamics determine tumor fate. From tumor cells themselves, with their capacity for unlimited replication, migration, and invasion, to fibroblasts, endothelial cells, and immune cells, which can have pro and/or anti-tumor potential, interaction among these elements determines tumor progression. The understanding of molecular pathways involved in immune escape has permitted the development of cancer immunotherapies. Targeting molecules or biological processes that inhibit antitumor immune responses has allowed a significant improvement in cancer patient’s prognosis. Autophagy is a cellular process required to eliminate dysfunctional proteins and organelles, maintaining cellular homeostasis. Usually a process associated with protection against cancer, autophagy associated to cancer cells has been reported in response to hypoxia, nutrient deficiency, and oxidative stress, conditions frequently observed in the TME. Recent studies have shown a paradoxical association between autophagy and tumor immune responses. Tumor cell autophagy increases the expression of inhibitory molecules, such as PD-1 and CTLA-4, which block antitumor cytotoxic responses. Moreover, it can also directly affect antitumor immune responses by, for example, degrading NK cell-derived granzyme B and protecting tumor cells. Interestingly, the activation of autophagy on dendritic cells has the opposite effects, enhancing antigen presentation, triggering CD8+ T cells cytotoxic activity, and reducing tumor growth. Therefore, this review will focus on the most recent aspects of autophagy and tumor immune environment. We describe the dual role of autophagy in modulating tumor immune responses and discuss some aspects that must be considered to improve cancer treatment.

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“…Increased numbers of CD8 þ T cells are crucial to the response to immunotherapy 19 and are associated with excellent clinical outcomes. 20 Detailed patient information is listed in Table 1. MHC-I expression and CD8 þ T cell infiltration were determined by immunohistochemistry (Figure 4b, c), and shown to be highly correlated: R 2 ¼ 0.713 (Figure 4a).…”

Section: Expression Of Mhc-i Positively Correlated With the Infiltrat...mentioning

confidence: 99%

Radiotherapy activates autophagy to increase CD8⁺ T cell infiltration by modulating major histocompatibility complex class-I expression in non-small cell lung cancer

et al. 2019

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Objective Radiotherapy is reported to enhance immune responses in cancer, but appropriate doses and mechanisms remain to be investigated. This study explored whether autophagy is involved in the regulation of major histocompatibility complex class I (MHC-I) expression and CD8+ T cell infiltration at different radiation doses. Methods Non-small cell lung cancer (NSCLC) cell lines A549 and H1975 were exposed to different doses of radiation. The levels of autophagy and MHC-I expression were examined 6 hours after irradiation. The effects of the autophagy inhibitor chloroquine (CQ) on MHC-I expression were also investigated, as well as the relationship between autophagy and MHC-1 expression. Pathological specimens from 69 NSCLC patients were collected, and immunohistochemistry was used to detect MHC-1 expression and CD8+ T cell infiltration in tumors. Results Irradiation induced autophagy and MHC-I expression during a single radiation dose from 2 to 20 Gy in a dose-dependent manner. CQ downregulated MHC-I expression. Immunohistochemistry indicated that MHC-I levels were positively correlated with the infiltration of CD8+ T cells in NSCLC cells (R2 = 0.713). Conclusions Autophagy induced MHC-I expression and increased CD8+ T cell infiltration. A single radiation dose of 20 Gy induced the strongest CD8+ T cell infiltration.

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Radiation Enhances the Efficacy of Antitumor Immunotherapy with an Immunocomplex of Interleukin-2 and its Monoclonal Antibody

Abstract: Radiation combined with IL-2/S4B6 may be a potential therapeutic option for therapy of osteosarcoma.

Cited by 6 publications

References 34 publications

Immunotherapy in soft tissue and bone sarcoma: unraveling the barriers to effectiveness

Immunotherapy in soft tissue and bone sarcoma: unraveling the barriers to effectiveness

The Role of Autophagy in Tumor Immunology—Complex Mechanisms That May Be Explored Therapeutically

Radiotherapy activates autophagy to increase CD8⁺ T cell infiltration by modulating major histocompatibility complex class-I expression in non-small cell lung cancer

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Radiation Enhances the Efficacy of Antitumor Immunotherapy with an Immunocomplex of Interleukin-2 and its Monoclonal Antibody

Abstract: Radiation combined with IL-2/S4B6 may be a potential therapeutic option for therapy of osteosarcoma.

Cited by 6 publications

References 34 publications

Immunotherapy in soft tissue and bone sarcoma: unraveling the barriers to effectiveness

Immunotherapy in soft tissue and bone sarcoma: unraveling the barriers to effectiveness

The Role of Autophagy in Tumor Immunology—Complex Mechanisms That May Be Explored Therapeutically

Radiotherapy activates autophagy to increase CD8+ T cell infiltration by modulating major histocompatibility complex class-I expression in non-small cell lung cancer

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Radiotherapy activates autophagy to increase CD8⁺ T cell infiltration by modulating major histocompatibility complex class-I expression in non-small cell lung cancer