Overcoming anti-PD-1/PD-L1 immune checkpoint blockade resistance: the role of macrophage, neutrophils and mast cells in the tumor microenvironment

Kwantwi, Louis Boafo

doi:10.1007/s10238-023-01059-4

Cited by 13 publications

(6 citation statements)

References 124 publications

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“…At the hepatic site, monocyte-derived macrophages induce apoptosis of tumorspecific CD8+ T cells, resulting in depletion from the peripheral circulation, leading to local and systemic resistance to ICI [23]. Therefore, macrophages are being discussed as novel targets to overcome therapy resistance [28]. One therapeutic approach directs against the scavenger receptor Stab1 [28], with a cell-specific expression only on subsets of macrophages and sinusoidal endothelial cells [1][2][3].…”

Section: Discussionmentioning

confidence: 99%

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Deficiency of Stabilin-1 in the Context of Hepatic Melanoma Metastasis

Wohlfeil,

Olsavszky,

Irkens

et al. 2024

Cancers

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Background: This study analyzed the role of Stabilin-1 on hepatic melanoma metastasis in preclinical mouse models. Methods: In Stabilin-1−/− mice (Stab1 KO), liver colonization of B16F10 luc2 and Wt31 melanoma was investigated. The numbers, morphology, and vascularization of hepatic metastases and the hepatic microenvironment were analyzed by immunofluorescence. Results: While hepatic metastasis of B16F10 luc2 or Wt31 melanoma was unaltered between Stab1 KO and wildtype (Ctrl) mice, metastases of B16F10 luc2 tended to be smaller in Stab1 KO. The endothelial differentiation of both types of liver metastases was similar in Stab1 KO and Ctrl. No differences in initial tumor cell adhesion and retention to the liver vasculature were detected in the B16F10 luc2 model. Analysis of the immune microenvironment revealed a trend towards higher levels of CD45+Gr-1+ cells in Stab1 KO as compared to Ctrl in the B16F10 luc2 model. Interestingly, significantly higher levels of POSTN were found in the matrix of hepatic metastases of Wt31, while liver metastases of B16F10 luc2 showed a trend towards increased deposition of RELN. Conclusions: Hepatic melanoma metastases show resistance to Stabilin-1 targeting approaches. This suggests that anti-Stab1 therapies should be considered with respect to the tumor entity or target organs.

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Section: Discussionmentioning

confidence: 99%

“…Therefore, macrophages are being discussed as novel targets to overcome therapy resistance [28]. One therapeutic approach directs against the scavenger receptor Stab1 [28], with a cell-specific expression only on subsets of macrophages and sinusoidal endothelial cells [1][2][3].…”

Section: Discussionmentioning

confidence: 99%

Deficiency of Stabilin-1 in the Context of Hepatic Melanoma Metastasis

Wohlfeil,

Olsavszky,

Irkens

et al. 2024

Cancers

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“…Despite blocking PD-1/PD-L1, tumor cells can still counter the immune checkpoints’ activity by activating additional inhibitory pathways. This occurs through the expression of other immune checkpoints and their ligands within the tumor’s immune microenvironment ( Kwantwi, 2023 ). Given that TAMs are an important component in the TME, and there is intricate relationship between TAMs and the PD-1/PD-L1 axis, TAMs will play a pivotal role in the resistance to anti-PD-1/PD-L1.…”

Section: The Role Of Tams In Resistance To Anti-pd-1/pd-l1 Immunother...mentioning

confidence: 99%

“…TAMs have been shown to promote the formation of extracellular matrix ( Afik et al, 2016 ), and the poor migration and infiltration of CD8 + T cells into tumor islets is a result of prolonged interaction with TAMs, which can trap lymphocytes ( Peranzoni et al, 2018 ). TAMs control the recruitment of T cells and induce their exclusion within the tumor, thereby contributing to anti-PD-1/PD-L1 resistance ( Kwantwi, 2023 ). Quaranta et al have identified granulin as potentially involved in the specific mechanism of inhibiting the migration of CD8 + T cells to tumor nests mediated by TAMs ( Quaranta et al, 2018 ).…”

Section: The Role Of Tams In Resistance To Anti-pd-1/pd-l1 Immunother...mentioning

confidence: 99%

Tumor-associated macrophages in anti-PD-1/PD-L1 immunotherapy for hepatocellular carcinoma: recent research progress

Li,

Duan,

et al. 2024

Front. Pharmacol.

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Hepatocellular carcinoma (HCC) is one of the cancers that seriously threaten human health. Immunotherapy serves as the mainstay of treatment for HCC patients by targeting the programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) axis. However, the effectiveness of anti-PD-1/PD-L1 treatment is limited when HCC becomes drug-resistant. Tumor-associated macrophages (TAMs) are an important factor in the negative regulation of PD-1 antibody targeted therapy in the tumor microenvironment (TME). Therefore, as an emerging direction in cancer immunotherapy research for the treatment of HCC, it is crucial to elucidate the correlations and mechanisms between TAMs and PD-1/PD-L1-mediated immune tolerance. This paper summarizes the effects of TAMs on the pathogenesis and progression of HCC and their impact on HCC anti-PD-1/PD-L1 immunotherapy, and further explores current potential therapeutic strategies that target TAMs in HCC, including eliminating TAMs in the TME, inhibiting TAMs recruitment to tumors and functionally repolarizing M2-TAMs (tumor-supportive) to M1-TAMs (antitumor type).

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“…For instance, only a subset of patients, approximately 20% to 25%, with lung cancer exhibit a durable response to immune checkpoint inhibitors (ICIs) [14]. Indeed, the complexity of the tumor microenvironment is thought to be a key factor contributing to the variable response rates observed with immune checkpoint inhibitors and, thus, the unsatisfactory outcomes in some patients [15]. Hence, there is a pressing need to identify and explore new targets to broaden the range of effective immunotherapies.…”

Section: Introductionmentioning

confidence: 99%

Identification of SEC61G as a Diagnostic and Prognostic Biomarker in Oral Squamous Cell Carcinoma

Zhang,

Chen,

et al. 2023

Biomedicines

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Oral squamous cell carcinoma (OSCC) is a heterogeneous malignancy originating from the oral mucosal epithelium. Detecting novel biomarkers can offer crucial information on disease aggressiveness and expected clinical outcomes for individual patients. SEC61G, an aberrantly expressed gene in various cancers, has been associated with negative clinical outcomes. However, its expression and clinical significance in OSCC is still unclear. In the present study, we investigated the SEC61G expression level in OSCC using bioinformatic and immunohistochemical analyses. Additionally, our findings revealed a significant correlation between SEC61G expression and clinicopathological characteristics, as well as a worse prognosis in OSCC patients. Notably, flow cytometry analysis on patient samples revealed that SEC61G expression was also linked to decreased immune infiltration in OSCC patients. In conclusion, our study provides evidence supporting SEC61G’s role as a potential diagnostic, prognostic, and therapeutic marker in OSCC.

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Overcoming anti-PD-1/PD-L1 immune checkpoint blockade resistance: the role of macrophage, neutrophils and mast cells in the tumor microenvironment

Cited by 13 publications

References 124 publications

Deficiency of Stabilin-1 in the Context of Hepatic Melanoma Metastasis

Deficiency of Stabilin-1 in the Context of Hepatic Melanoma Metastasis

Tumor-associated macrophages in anti-PD-1/PD-L1 immunotherapy for hepatocellular carcinoma: recent research progress

Identification of SEC61G as a Diagnostic and Prognostic Biomarker in Oral Squamous Cell Carcinoma

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