Anti-4-1BB immunotherapy enhances systemic immune effects of radiotherapy to induce B and T cell-dependent anti-tumor immune activation and improve tumor control at unirradiated sites

Martin, Alexandra; Powell, Chase; Nagy, Mate; Innamarato, Patrick; Powers, John J.; Nichols, Derek A.; Anadon, Carmen M.; Chaurio, Ricardo A.; Kim, Sungjune; Wang, Min-Hsuan; Gong, Beini; Wang, Xianzhe; Scheutz, Thomas J; Antonia, Scott; Conejo-García, José R.; Perez, Bradford A.

doi:10.1007/s00262-022-03325-y

Cited by 5 publications

(3 citation statements)

References 69 publications

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“…46 B and T cells play a vital part in antitumor immunity in SCLC. 47 We showed that, in response to chemotherapy, both types of immune cells exhibited an activated phenotype: complement and interferon were upregulated in plasma cells, while interferon-α and -γ increased in T cells. Chemotherapy also increased the functional diversity of CD8 + T cells, accompained by upregulation of interferon signaling, which mediates antitumor responses in lung cancer.…”

Section: Discussionmentioning

confidence: 91%

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Single‐cell transcriptome analysis reveals cellular and molecular alterations in small cell lung cancer tumors following chemotherapy

成晟

Zhu

et al. 2023

Intl Journal of Cancer

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Chemotherapy is the standard therapy for small cell lung cancer (SCLC), but relapse is common and the 2-year survival rate remains low. Given the contribution of the tumor microenvironment (TME) to cancer development and response to treatment, we analyzed here how chemotherapy alters the TME in SCLC using single-cell RNA sequencing. The comparison between neuroendocrine cells and other epithelial cells in fivechemotherapy-naive patients identified upregulation of Notch-inhibiting genes, such as DLL3 and HES6. Analysis of genes differentially expressed between five patients receiving chemotherapy and five treatment-naive patients in cells in the TME showed that chemotherapy promoted antigen presentation and senescence in neuroendocrine cells, upregulated ID1 to enhance angiogenic activities of stalk-like endothelial cells and strengthened vascular endothelial growth factor signaling in lymphatic endothelial cells.Chemotherapy also promoted the remodeling of extracellular matrix by fibroblasts and upregulated interferon-mediated antitumor immune responses by B and T cells. Our single-cell transcriptome analysis provides insights into how chemotherapy affects the TME in SCLC, which may guide efforts to make therapy more effective.

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Section: Discussionmentioning

confidence: 91%

“…B and T cells play a vital part in antitumor immunity in SCLC 47 . We showed that, in response to chemotherapy, both types of immune cells exhibited an activated phenotype: complement and interferon were upregulated in plasma cells, while interferon‐α and ‐γ increased in T cells.…”

Section: Discussionmentioning

confidence: 97%

Single‐cell transcriptome analysis reveals cellular and molecular alterations in small cell lung cancer tumors following chemotherapy

成晟

Zhu

et al. 2023

Intl Journal of Cancer

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“…Therefore, significant antitumor immunity may be generated by combining RT and the targeting of multiple stimulatory and/or inhibitory checkpoints. This strategy may be further explored in the context of combining RT with dual immune checkpoint blockade (ICB) (207)(208)(209)(210)(211)(212).…”

Section: Augmenting Antitumor Immunity By Combining Radiotherapy With...mentioning

confidence: 99%

Mechanistic rationales for combining immunotherapy with radiotherapy

Chi

Nguyen

2023

Front. Immunol.

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Immunotherapy consisted mainly of immune checkpoint inhibitors (ICIs) has led to significantly improved antitumor response. However, such response has been observed only in tumors possessing an overall responsive tumor immune micro-environment (TIME), in which the presence of functional tumor-infiltrating lymphocytes (TILs) is critical. Various mechanisms of immune escape from immunosurveillance exist, leading to different TIME phenotypes in correlation with primary or acquired resistance to ICIs. Radiotherapy has been shown to induce antitumor immunity not only in the irradiated primary tumor, but also at unirradiated distant sites of metastases. Such antitumor immunity is mainly elicited by radiation’s stimulatory effects on antigenicity and adjuvanticity. Furthermore, it may be significantly augmented when irradiation is combined with immunotherapy, such as ICIs. Therefore, radiotherapy represents one potential therapeutic strategy to restore anti-tumor immunity in tumors presenting with an unresponsive TIME. In this review, the generation of anti-tumor immunity, its impairment, radiation’s immunogenic properties, and the antitumor effects of combining radiation with immunotherapy will be comprehensively discussed.

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A novel agonist of 4-1BB costimulatory receptor shows therapeutic efficacy against a tobacco carcinogen-induced lung cancer

Gulen,

Rudraboina,

Tarique

et al. 2023

Cancer Immunol Immunother

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Anti-4-1BB immunotherapy enhances systemic immune effects of radiotherapy to induce B and T cell-dependent anti-tumor immune activation and improve tumor control at unirradiated sites

Cited by 5 publications

References 69 publications

Single‐cell transcriptome analysis reveals cellular and molecular alterations in small cell lung cancer tumors following chemotherapy

Single‐cell transcriptome analysis reveals cellular and molecular alterations in small cell lung cancer tumors following chemotherapy

Mechanistic rationales for combining immunotherapy with radiotherapy

A novel agonist of 4-1BB costimulatory receptor shows therapeutic efficacy against a tobacco carcinogen-induced lung cancer

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