Improving efficacy of cancer immunotherapy through targeting of macrophages

Peranzoni, Elisa; Donnadieu, Emmanuel

doi:10.1080/21645515.2018.1515447

Cited by 11 publications

(9 citation statements)

References 27 publications

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“…Previous studies have also demonstrated that stromal TAMs have long-lasting interactions with stromal T cells, 'trapping' them in the stroma and preventing them from gaining access to the tumour cells [49]. Our findings suggest that the therapeutic targeting of TAMs may be important in enabling CD8 + cells to access the tumour, further enhancing and synergising current immune checkpoint-based immunotherapy in ARID1A mutant patients [42][43][44][45][46][47][48][49][50]. Known synthetic-lethal targeting strategies associated with ARID1A deficiency, such as ATR inhibitors and/or PARP inhibitors , may also help prime the immune system and synergise the immune checkpoint blockade.…”

Section: Discussionsupporting

confidence: 57%

Quantitative Assessment and Prognostic Associations of the Immune Landscape in Ovarian Clear Cell Carcinoma

Khalique

Nash

Mansfield

et al. 2021

Cancers

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Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer characterised by a high frequency of loss-of-function ARID1A mutations and a poor response to chemotherapy. Despite their generally low mutational burden, an intratumoural T cell response has been reported in a subset of OCCC, with ARID1A purported to be a biomarker for the response to the immune checkpoint blockade independent of micro-satellite instability (MSI). However, assessment of the different immune cell types and spatial distribution specifically within OCCC patients has not been described to date. Here, we characterised the immune landscape of OCCC by profiling a cohort of 33 microsatellite stable OCCCs at the genomic, gene expression and histological level using targeted sequencing, gene expression profiling using the NanoString targeted immune panel, and multiplex immunofluorescence to assess the spatial distribution and abundance of immune cell populations at the protein level. Analysis of these tumours and subsequent independent validation identified an immune-related gene expression signature associated with risk of recurrence of OCCC. Whilst histological quantification of tumour-infiltrating lymphocytes (TIL, Salgado scoring) showed no association with the risk of recurrence or ARID1A mutational status, the characterisation of TILs via multiplexed immunofluorescence identified spatial differences in immunosuppressive cell populations in OCCC. Tumour-associated macrophages (TAM) and regulatory T cells were excluded from the vicinity of tumour cells in low-risk patients, suggesting that high-risk patients have a more immunosuppressive microenvironment. We also found that TAMs and cytotoxic T cells were also excluded from the vicinity of tumour cells in ARID1A-mutated OCCCs compared to ARID1A wild-type tumours, suggesting that the exclusion of these immune effectors could determine the host response of ARID1A-mutant OCCCs to therapy. Overall, our study has provided new insights into the immune landscape and prognostic associations in OCCC and suggest that tailored immunotherapeutic approaches may be warranted for different subgroups of OCCC patients.

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Section: Discussionsupporting

confidence: 57%

Quantitative Assessment and Prognostic Associations of the Immune Landscape in Ovarian Clear Cell Carcinoma

Khalique

Nash

Mansfield

et al. 2021

Cancers

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“…Given the impact of myeloid cells on immunotherapy reported in the previous paragraphs, it seems reasonable to combine ICIs with drugs that target these subsets (3,5,7). A huge amount of preclinical data supports this hypothesis and the relevance of these combinations is also emerging in the clinic.…”

Section: Combination Strategies For Improving Ici Therapy By Targetinmentioning

confidence: 92%

“…Depending on the TME, these myeloid populations can adopt very different phenotypes with distinct impact on the anti-tumor immune response, angiogenesis and invasion. Many reviews have analyzed the influence of tumor-infiltrating myeloid cells on the prognosis of cancer patients ( 32 – 35 ) and the mechanisms of negative and positive regulation of the anti-tumor immune response ( 3 , 4 , 36 ). Although most findings come from murine tumors, some clinical data are emerging that link the presence of myeloid cells in the TME with the outcome of approved immune checkpoint therapies, as discussed later ( 6 – 8 ).…”

Section: Biomarkers In Ici Therapymentioning

confidence: 99%

“…Not surprisingly, biomarkers are currently mainly focused on T cells and tumor cells, but it is becoming clear that other cell types in the periphery and at the tumor site can impact the efficacy of immunotherapy. Myeloid cells are among the "usual suspects, " given their plasticity and their well-known role as immune modulators in tumor growth and metastasis (2)(3)(4)(5). The modulation of ICI response by cells of the myeloid lineage is currently being examined, mainly at the preclinical level.…”

Section: Introductionmentioning

confidence: 99%

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Myeloid Cells as Clinical Biomarkers for Immune Checkpoint Blockade

et al. 2020

Self Cite

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Immune checkpoint inhibitors are becoming standard treatments in several cancer types, profoundly changing the prognosis of a fraction of patients. Currently, many efforts are being made to predict responders and to understand how to overcome resistance in non-responders. Given the crucial role of myeloid cells as modulators of T effector cell function in tumors, it is essential to understand their impact on the clinical outcome of immune checkpoint blockade and on the mechanisms of immune evasion. In this review we focus on the existing clinical evidence of the relation between the presence of myeloid cell subsets and the response to anti-PD(L)1 and anti-CTLA-4 treatment. We highlight how circulating and tumor-infiltrating myeloid populations can be used as predictive biomarkers for immune checkpoint inhibitors in different human cancers, both at baseline and on treatment. Moreover, we propose to follow the dynamics of myeloid cells during immunotherapy as pharmacodynamic biomarkers. Finally, we provide an overview of the current strategies tested in the clinic that use myeloid cell targeting together with immune checkpoint blockade with the aim of uncovering the most promising approaches for effective combinations.

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“…Increasing evidence suggest that cytokines secreted by TAMs can induce anti-apoptotic, hyperproliferative and metastatic responses in lung cancer (9)(10)(11). TAMs can weaken the immunotherapy by impede T cells from reaching tumor cells (12). Targeting TAMs may treat as a possible therapeutic strategy to improve T cell interaction with cancer cells, thereby shifting "immuneexcluded" tumors, which are refractory to immune checkpoint inhibitors, into tumors that respond to anti-PD-1 antibodies (12).…”

Section: Introductionmentioning

confidence: 99%

LAMC2 promotes the proliferation of cancer cells and induce infiltration of macrophages in non-small cell lung cancer

Liu¹,

Cai²,

Xia³

et al. 2021

Ann Transl Med

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Background: Non-small-cell lung cancer (NSCLC) is the most prevalent cancer worldwide. Tumor microenvironment (TME) plays a very important role in the cancer development. Thus, it is urgent to find the change of TME that contributes to NSCLC carcinogenesis and progression. Methods:The bioinformatics analysis approach was applied to evaluate the change of TME and screen the differentially immune cells in NSCLC tissue based on The Cancer Genome Atlas (TCGA) data.Meanwhile, the association of differentially immune cells with tumor stage and prognosis of NSCLC was evaluated. Then, we screen the different expression genes between macrophages infiltration high group and low group. After that, the expression of LAMC2 was detected in 48 cases of NSCLC tissues and paired normal tissues. The function of LAMC2 was detected through cell experiments in vitro. Immunohistochemistry assay was used to detect the correlation between LAMC2 expression and macrophages infiltration in NSCLC tissue. LAMC2-related pathways were identified by gene set enrichment analysis.Results: Compared with early stage, middle-advanced stage of NSCLC exhibited lower immune score.Macrophages were the main component of different immune cells and correlated with poor outcome. The results of immunohistochemistry indicated that the expression of LAMC2 in NSCLC tissues was higher than paired normal tissues. Down-regulation of LAMC2 inhibited the proliferation, migration and invasion of NSCLC cells in vitro. Overexpression of LAMC2 was positively associated with macrophages infiltration in NSCLC tissues. Inhibition of LAMC2 expression in NSCLC cells could reduce THP-1 infiltration, and LAMC2 protein could promote the infiltration of THP-1. The Gene Set Enrichment Analysis results showed that high expression of LAMC2 was correlated with focal adhesion and extracellular matrix receptor interaction.Conclusions: Immune suppression and macrophages infiltration were correlated with poor outcomes in NSCLC. LAMC2 promoted macrophages infiltration and extracellular matrix remolding in NSCLC. Our studies suggested an oncogenic role of LAMC2 in NSCLC progression and it perhaps serve as a potential immune therapy target for NSCLC.

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Improving efficacy of cancer immunotherapy through targeting of macrophages

Cited by 11 publications

References 27 publications

Quantitative Assessment and Prognostic Associations of the Immune Landscape in Ovarian Clear Cell Carcinoma

Quantitative Assessment and Prognostic Associations of the Immune Landscape in Ovarian Clear Cell Carcinoma

Myeloid Cells as Clinical Biomarkers for Immune Checkpoint Blockade

LAMC2 promotes the proliferation of cancer cells and induce infiltration of macrophages in non-small cell lung cancer

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