Cytokines chattering in pancreatic ductal adenocarcinoma tumor microenvironment

Bhatia, Rakesh; Bhyravbhatla, Namita; Kisling, Andrew; Li, Xiaoqi; Batra, Surinder K.; Kumar, Sushil

doi:10.1016/j.semcancer.2022.03.021

Cited by 21 publications

(9 citation statements)

References 143 publications

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“…The cytokine interleukin-1 α (IL-1 α) promotes the survival of breast cancer cells by inducing the expression of the key tumor survival-promoting cytokine, TSLP 33 . Cytokines in the TME facilitate tumorigenesis, progression, metastasis, and distant colonization of malignant cells in pancreatic ductal adenocarcinoma through their receptors 34 . The immunological effect of IFN-γ, an immunoactive cytokine, on carcinogenesis in TME is unclear.…”

Section: Discussionmentioning

confidence: 99%

Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells

Jing,

Liu,

Zhou

et al. 2024

Sci Rep

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The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8+ T cells and accelerating apoptosis in CD8+ T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells.

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Section: Discussionmentioning

confidence: 99%

Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells

Jing,

Liu,

Zhou

et al. 2024

Sci Rep

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“…Cytokines promote PDAC initiation, progression, metastasis, and the distant colonization of malignant cells via their receptors. These signaling mediators secreted by TAMs and CAFs, combined with oncogenic KRAS mutations, initiate ductal metaplasia in progenitors, thus resulting in the appearance of early preneoplastic lesions ( Bhatia et al ., 2022 ). The proinflammatory cytokine IL-1β has two roles.…”

Section: Innate Immune Systemmentioning

confidence: 99%

Tumor Stroma as a Therapeutic Target for Pancreatic Ductal Adenocarcinoma

Lee,

Han,

Jung

et al. 2024

Biomol Ther (Seoul)

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Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis owing to its desmoplastic stroma. Therefore, therapeutic strategies targeting this tumor stroma should be developed. In this study, we describe the heterogeneity of cancer-associated fibroblasts (CAFs) and their diverse roles in the progression, immune evasion, and resistance to treatment of PDAC. We subclassified the spatial distribution and functional activity of CAFs to highlight their effects on prognosis and drug delivery. Extracellular matrix components such as collagen and hyaluronan are described for their roles in tumor behavior and treatment outcomes, implying their potential as therapeutic targets. We also discussed the roles of extracellular matrix (ECM) including matrix metalloproteinases and tissue inhibitors in PDAC progression. Finally, we explored the role of the adaptive and innate immune systems in shaping the PDAC microenvironment and potential therapeutic strategies, with a focus on immune cell subsets, cytokines, and immunosuppressive mechanisms. These insights provide a comprehensive understanding of PDAC and pave the way for the development of prognostic markers and therapeutic interventions.

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“…After receiving antigens presented by DCs and TAMs, the signal transmission and function of T cells largely determine the efficiency of cancer immunotherapy. [38][39][40][41] However, the "immune-cold" nature of CHOL makes it difficult for traditional photodynamic immunotherapy to stimulate adequate adaptive immune responses to the extent of producing ideal therapeutic effect (Figure S13, Supporting Information). In order to confirm the enhanced photodynamic immunotherapy effect of p-Adv-CAT-KR on activating adaptive immunity, experiments with full scale were performed, involving infiltration, phenotypic differentiation, and cytokine secretion of T cells in Figure 6.…”

Section: P-adv-cat-kr-mediated Adaptive Immune Stimulation Via Pd-1/p...mentioning

confidence: 99%

Three‐in‐One Oncolytic Adenovirus System Initiates a Synergetic Photodynamic Immunotherapy in Immune‐Suppressive Cholangiocarcinoma

Wang

Zhu

Chen

et al. 2023

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Although photodynamic immunotherapy has been promoted in the clinical practice of cholangiocarcinoma, the insensitivity to photodynamic immunotherapy remains to be a great problem. This can be largely attributed to an immune‐suppressive tumor microenvironment (TME) manifested as immature myeloid cells and exhausted cytotoxic T lymphocytes. Here, a three‐in‐one oncolytic adenovirus system PEG‐PEI‐Adv‐Catalase‐KillerRed (p‐Adv‐CAT‐KR) has been constructed to multiply, initiate, and enhance immune responses in photodynamic immunotherapy, using genetically‐engineered KillerRed as photosensitizer, catalase as in situ oxygen‐supplying mediator, and adenovirus as immunostimulatory bio‐reproducible carrier. Meanwhile, PEG‐PEI is applied to protect adenovirus from circulating immune attack. The administration of p‐Adv‐CAT‐KR induces increased antigen presenting cells, elevated T cell infiltrations, and reduced tumor burden. Further investigation into underlying mechanism indicates that hypoxia inducible factor 1 subunit alpha (Hif‐1α) and its downstream PD‐1/PD‐L1 pathway contribute to the transformation of immune‐suppressive TME in cholangiocarcinoma. Collectively, the combination of KillerRed, catalase, and adenovirus brings about multi‐amplified antitumor photo‐immunity and has the potential to be an effective immunotherapeutic strategy for cholangiocarcinoma.

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Cytokines chattering in pancreatic ductal adenocarcinoma tumor microenvironment

Cited by 21 publications

References 143 publications

Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells

Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells

Tumor Stroma as a Therapeutic Target for Pancreatic Ductal Adenocarcinoma

Three‐in‐One Oncolytic Adenovirus System Initiates a Synergetic Photodynamic Immunotherapy in Immune‐Suppressive Cholangiocarcinoma

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