Genome and Transcriptome Biomarkers of Response to Immune Checkpoint Inhibitors in Advanced Solid Tumors

Pender, Alexandra; Titmuss, Emma; Pleasance, Erin; Fan, Kevin; Pearson, Hillary; Brown, Scott D.; Grisdale, Cameron J.; Topham, James T.; Shen, Yaoqing; Bonakdar, Melika; Taylor, Gregory A.; Williamson, Laura; Mungall, Karen; Chuah, Eric; Moore, Richard A.; Lavoie, Jean‐Michel; Yip, Stephen; Lim, Howard John; Renouf, Daniel J.; Sun, Sophie; Holt, Robert A.; Jones, Steven J.M.; Marra, Marco A.; Laskin, Janessa

doi:10.1158/1078-0432.ccr-20-1163

Cited by 64 publications

(76 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-34 and M-CSF can induce macrophages to differentiate into the M2 type, leading to immune suppression mediated by M2 macrophages (37). It is worth noting that M2 macrophages are generally considered cancer-promoting, which seems to differ from our results, and the reasons for this need to be explored (38,39). IL-34 is related to PD-L1 expression and the PD-1 signaling pathway.…”

Section: Discussioncontrasting

confidence: 56%

Loss of IL-34 Expression Indicates Poor Prognosis in Patients With Lung Adenocarcinoma

et al. 2021

View full text Add to dashboard Cite

Interleukin 34 (IL-34), an additional ligand of the colony-stimulating factor-1 receptor (CSF-1R), promotes the secretion of pro-inflammatory cytokines and stimulates NF-κB and JNK-related signaling pathways. However, the potential mechanism and prognostic value of IL-34 in lung adenocarcinoma (LUAD) remain obscure. In this study, IL-34 was found to be downregulated in LUAD tissues compared with para-carcinoma tissues, and loss of IL-34 expression was correlated with shorter overall survival (OS), which was validated by bioinformatics\ analysis in TCGA (The Cancer Genome Atlas) cohort and immunohistochemical analysis in the NTU (Nantong University) cohort, respectively. Subsequently, loss of IL-34 promotes negative regulation of the immune system and inhibits the infiltration of immune cells. Moreover, IL-34 deficiency was shown to be an independent adverse prognostic factor for patients with LUAD, and subgroup analysis indicated that IL-34 might contribute to the stratified management of patients with LUAD. IL-34-based nomogram model significantly improved the accuracy of prognostic predictions for OS of patients with LUAD, both in the TCGA cohort and the NTU cohort. Taken together, our data suggested that loss of IL-34 expression is associated with poor prognosis and negative regulation of the immune system of patients with LUAD, contributing to the stratified management of patients with LUAD.

show abstract

Section: Discussioncontrasting

confidence: 56%

Loss of IL-34 Expression Indicates Poor Prognosis in Patients With Lung Adenocarcinoma

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Another study, investigating renal cell carcinoma tissues from patients treated with a combination of anti-PD-L1 and anti-VEGF-A mAbs (atezolizumab and bevacizumab, respectively) revealed a correlation between a high T effector gene signature and an improved overall response rate and progression-free survival, while a high myeloid inflammation gene signature was associated with a reduced progression-free survival [ 28 ]. Furthermore, in advanced solid tumors the M1/M2 macrophage ratio score together with the tumor mutational burden and CD8+ scores were all predictors of response to ICIs [ 29 ].…”

Section: From Circulating Monocytes To Tumor-associated Macrophagementioning

confidence: 99%

Targeting Tumor-Associated Macrophages to Increase the Efficacy of Immune Checkpoint Inhibitors: A Glimpse into Novel Therapeutic Approaches for Metastatic Melanoma

Ceci

Atzori

Lacal

et al. 2020

Cancers

View full text Add to dashboard Cite

Immune checkpoint inhibitors (ICIs) represent a promising therapeutic intervention for a variety of advanced/metastatic solid tumors, including melanoma, but in a large number of cases, patients fail to establish a sustained anti-tumor immunity and to achieve a long-lasting clinical benefit. Cells of the tumor micro-environment such as tumor-associated M2 macrophages (M2-TAMs) have been reported to limit the efficacy of immunotherapy, promoting tumor immune evasion and progression. Thus, strategies targeting M2-TAMs have been suggested to synergize with immune checkpoint blockade. This review recapitulates the molecular mechanisms by which M2-TAMs promote cancer immune evasion, with focus on the potential cross-talk between pharmacological interventions targeting M2-TAMs and ICIs for melanoma treatment.

show abstract

“…After abstract review, we identified 34 articles for full manuscript review and 28 of these articles were excluded for the reasons delineated in Figure 1. Finally, nine studies from six articles (23,(28)(29)(30)(31)(32) were included in the final meta-analysis (Table 1).…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

Prognostic Impact of Memory CD8(+) T Cells on Immunotherapy in Human Cancers: A Systematic Review and Meta-Analysis

et al. 2021

View full text Add to dashboard Cite

ObjectiveThe objective of this systematic review and meta-analysis was to determine the prognostic value of memory CD8(+) T cells in cancer patients with immunotherapy.MethodsEMBASE, MEDLINE (PubMed), and Web of Science databases were searched to identify suitabile articles published before March 2021. Risk of bias on the study level was assessed using the Cochrane Bias Risk Assessment Tool. The hazard ratios (HRs) and 95% confidence intervals (CIs) of pooled progression-free survival (PFS) and overall survival (OS) were calculated using RevMan 5.4 to evaluate the prognostic impact of memory CD8(+) T cells.ResultsIn total, nine studies were included in the final analysis. High levels of memory CD8(+) T cells were significantly closely correlated with better progression-free survival (PFS) and overall survival (OS) of cancer patients with immunotherapy (PFS, HR 0.64, 95% CI 0.53–0.78; OS, HR 0.37, 95% CI 0.21–0.65). Memory CD8(+) T cells still have significant prognostic value in cancer patients given immunotherapy alone after excluding of other interfering factors such as chemotherapy, radiotherapy, and targeted therapy (PFS, HR 0.65, 95% CI 0.48–0.89; OS, HR 0.23, 95% CI 0.13–0.42). However, high memory CD8(+) T cells levels did not correspond to a longer PFS or OS in cancer patients with non-immunotherapy (PFS, HR 1.05, 95% CI 0.63–1.73; OS, HR 1.29, 95% CI 0.48–3.48). Thus, memory CD8(+) T cells might be a promising predictor in cancer patients with immunotherapy.ConclusionsThe host’s overall immune status, and not only the tumor itself, should be considered to predict the efficacy of immunotherapy in cancer patients. This study is the first to show the significant prognostic value of memory CD8(+) T cells in immunotherapy of cancer patients through systematic review and meta-analysis. Thus, the detection of memory CD8(+) T cells has a considerable value in clinical practice in cancer patients with immunotherapy. Memory CD8(+) T cells may be promising immunotherapy targets.

show abstract

Genome and Transcriptome Biomarkers of Response to Immune Checkpoint Inhibitors in Advanced Solid Tumors

Cited by 64 publications

References 53 publications

Loss of IL-34 Expression Indicates Poor Prognosis in Patients With Lung Adenocarcinoma

Loss of IL-34 Expression Indicates Poor Prognosis in Patients With Lung Adenocarcinoma

Targeting Tumor-Associated Macrophages to Increase the Efficacy of Immune Checkpoint Inhibitors: A Glimpse into Novel Therapeutic Approaches for Metastatic Melanoma

Prognostic Impact of Memory CD8(+) T Cells on Immunotherapy in Human Cancers: A Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About