Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer

Giatromanolaki, Alexandra; Mitrakas, Achilleas; Anestopoulos, Ioannis; Kontosis, Andreas; Koukourakis, Ioannis M; Pappa, Aglaia; Panayiotidis, Mihalis I.; Koukourakis, Michael I.

doi:10.3390/cancers14071801

Cited by 21 publications

(12 citation statements)

References 26 publications

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“…It may indicate that antigen-presenting activity of CD86 + cells may not play an essential role of antigen presentation in AD-G [23] . We also found the high CD47 expression in AD-G, which may indicate that tumors may evade macrophage phagocytosis via the CD47/SIRPα axis [24,25] . Furthermore, polarization pattern of macrophage may distinguish its function in tumor cells.…”

Section: Discussionmentioning

confidence: 53%

Multi-omics Research on the Heterogeneity and Immune Landscape of Lung Adenocarcinoma with Ground-glass opacity

Miao

Teng

et al. 2022

Preprint

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Background: Lung adenocarcinoma with ground-glass opacity (GGO) has been detected increasingly and now accounts for most lung cancer patients. Lung adenocarcinoma with GGO contains a complex ecosystem. The mechanism of lung adenocarcinoma with GGO remains largely elusive. We use mass spectrometry proteomics combined with metabolomics to understand how these characteristics achieve a long-term functional balance and the trend of changes in tumor progression at the cellular functional level. Methods: We initiated a prospective cohort study to characterize lung adenocarcinoma with GGO components or without GGO components. Tumor and para-cancer tissue samples were collected. Multi-omics including transcriptomics proteomics and metabonomics were performed. Results: We found lung adenocarcinoma with GGO had a relatively slow proliferation tumor cells and stronger immune cell infiltration in proteomic and transcriptomic analysis. The immune cell markers expression, including CD47, CD68, CD81, CD86, C1Q, SPP1, CXCL13, ALOX5AP and HPGD was found overexpression in lung adenocarcinoma with GGO, which indicated more immune cell infiltration. In metabolomic analysis, GAPDH, ENO1 and LDHA were highly expressed in pure-solid lung adenocarcinoma, and GPD1 was highly expressed in lung adenocarcinoma with GGO. The combined transcriptome and proteome analysis revealed that proteins with consistent differences mainly included GAPDH, MKI67, AGER, and CRYM. KEGG pathway enrichment analysis showed that several aliphatic acyclic compounds expression were higher in lung adenocarcinoma with GGO. Conclusion: We describe a functional homeostasis in lung adenocarcinoma with GGO, which was constructed by relatively slow proliferation tumor cells and stronger immune cell infiltration. Overexpression of CXCL13 drives the infiltration of immune cells, which means the formation of anti-tumor tertiary lymphatic structures. The dysfunction of macrophage may be an important marker of this progression.

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Section: Discussionmentioning

confidence: 53%

Multi-omics Research on the Heterogeneity and Immune Landscape of Lung Adenocarcinoma with Ground-glass opacity

Miao

Teng

et al. 2022

Preprint

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“…Firstly, high pre-treatment levels of sSIRPα could potentially signal a poor prognosis reflecting sSIRPα constitutively released by high numbers of TAMs. This is supported by SIRPα being constitutively released by MDMs and by recent evidence linking high SIRPα expression to poor survival in sev-eral tumors [11,[21][22][23][24]. Secondly, a rise in sSIRPα levels after initiation of immunotherapy may reflect the level of immune activation achieved, and thus predict the successfulness of the treatment.…”

Section: Discussionmentioning

confidence: 90%

A New Serum Macrophage Checkpoint Biomarker for Innate Immunotherapy: Soluble Signal-Regulatory Protein Alpha (sSIRPα)

et al. 2022

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Background and Aims: The macrophage “don’t eat me” pathway CD47/SIRPα is a target for promising new immunotherapy. We hypothesized that a soluble variant of SIRPα is present in the blood and may function as a biomarker. Methods: Monocyte derived macrophages (MDMs) from human buffy-coats were stimulated into macrophage subtypes by LPS and IFN-γ (M1), IL-4 and IL-13 (M2a), IL-10 (M2c) and investigated using flow cytometry. Soluble SIRPα (sSIRPα) was measured in cell cultures and serum by Western blotting and an optimized ELISA. Serum samples were obtained from 120 healthy individuals and from 8 individuals challenged by an LPS injection. Results: All macrophage phenotypes expressed SIRPα by flowcytometry, and sSIRPα was present in all culture supernatants including unstimulated cells. M1 macrophages expressed the lowest level of SIRPαand released the highest level of sSIRPα (p < 0.05). In vivo, the serum level of sSIRPα increased significantly (p < 0.0001) after an LPS challenge in humans. The median concentration in healthy individuals was 28.7 µg/L (19.8–41.1, 95% reference interval), and 20.5 µg/L in an IFCC certified serum reference material. The protein was stable in serum for prolonged storage and repeated freeze/thawing. Conclusions: We demonstrate that sSIRPα is produced constitutively and the concentration increases upon macrophage activation both in vitro and in vivo. It is present in human serum where it may function as a biomarker for the activity of tumor-associated macrophages (TAMs), and for monitoring the effect of immunotherapy.

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“…Improving the phagocytic activity of TAMs is becoming a new way for treating cancer. The CD47-SIRPα axis reduces ability of TAMs to recognize and phagocytose tumor cells [ 50 ] (Fig. 2 ).…”

Section: Tam-targeting Therapymentioning

confidence: 99%

Targeting tumor-associated macrophages for cancer treatment

Zhu

et al. 2022

Cell Biosci

114

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Tumor-associated macrophages (TAMs) are abundant, nearly accounting for 30–50% of stromal cells in the tumor microenvironment. TAMs exhibit an immunosuppressive M2-like phenotype in advanced cancer, which plays a crucial role in tumor growth, invasion and migration, angiogenesis and immunosuppression. Consequently, the TAM-targeting therapies are particularly of significance in anti-cancer strategies. The application of TAMs as anti-cancer targets is expected to break through traditional tumor-associated therapies and achieves favorable clinical effect. However, the heterogeneity of TAMs makes the strategy of targeting TAMs variable and uncertain. Discovering the subset specificity of TAMs might be a future option for targeting TAMs therapy. Herein, the review focuses on highlighting the different modalities to modulate TAM’s functions, including promoting the phagocytosis of TAMs, TAMs depletion, blocking TAMs recruitment, TAMs reprogramming and suppressing immunosuppressive tumor microenvironment. We also discuss about several ways to improve the efficacy of TAM-targeting therapy from the perspective of combination therapy and specificity of TAMs subgroups.

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Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer

Cited by 21 publications

References 26 publications

Multi-omics Research on the Heterogeneity and Immune Landscape of Lung Adenocarcinoma with Ground-glass opacity

Multi-omics Research on the Heterogeneity and Immune Landscape of Lung Adenocarcinoma with Ground-glass opacity

A New Serum Macrophage Checkpoint Biomarker for Innate Immunotherapy: Soluble Signal-Regulatory Protein Alpha (sSIRPα)

Targeting tumor-associated macrophages for cancer treatment

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