Tumor-Associated Macrophages Regulate PD-1/PD-L1 Immunosuppression

Pu, Yunzhou; Ji, Qing

doi:10.3389/fimmu.2022.874589

Cited by 133 publications

(80 citation statements)

References 134 publications

(119 reference statements)

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“…Accumulating evidence has indicated that TAMs in TME is associated with the prognosis and immunological characteristics of a variety of cancers (Lam et al, 2019;Li et al, 2019;Xiao N et al, 2021). TAMs can mediate PD-1 drug resistance in HCC through the PD-L1 pathway and regulation of T cells (Pu and Ji, 2022). Molecular biomarkers of TAMs could be used for risk-stratification and response prediction of cancer treatments, though the fundamental cognition of cellular structures and molecular landscapes in liver cancer remains difficult to define.…”

Section: Discussionmentioning

confidence: 99%

Construction of a tumor immune infiltration macrophage signature for predicting prognosis and immunotherapy response in liver cancer

Huang

Zhang

et al. 2022

Front. Mol. Biosci.

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Liver cancer is an extraordinarily heterogeneous malignant disease. The tumor microenvironment (TME) and tumor-associated macrophages (TAMs) are the major drivers of liver cancer initiation and progression. It is critical to have a better understanding of the complicated interactions between liver cancer and the immune system for the development of cancer immunotherapy. Based on the gene expression profiles of tumor immune infiltration cells (TIICs), upregulated genes in TAMs and downregulated genes in other types of immune cells were identified as macrophage-specific genes (MSG). In this study, we combined MSG, immune subtypes, and clinical information on liver cancer to develop a tumor immune infiltration macrophage signature (TIMSig). A four-gene signature (S100A9, SLC22A15, TRIM54, and PPARGC1A) was identified as the TAM-related prognostic genes for liver cancer, independent of multiple clinicopathological parameters. Survival analyses showed that patients with low TIMSig had a superior survival rate than those with high TIMSig. Additionally, clinical immunotherapy response and TIMSig was observed as highly relevant. In addition, TIMSig could predict the response to chemotherapy. Collectively, the TIMSig could be a potential tool for risk-stratification, clinical decision making, treatment planning, and oncology immunotherapeutic drug development.

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Section: Discussionmentioning

confidence: 99%

Construction of a tumor immune infiltration macrophage signature for predicting prognosis and immunotherapy response in liver cancer

Huang

Zhang

et al. 2022

Front. Mol. Biosci.

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“…We also observed phenotype shifting of TAMs from immune-suppressive CD68 + CD163 + TAM2 to pro-inflammatory/anti-tumor CD68 + CD163 - TAM1. TAM2 has long been recognized to be associated with tumor progression, metastasis and poor prognosis, and recent evidence revealed TAM2 suppressed the effect of ICIs via secreting anti-inflammatory cytokines and exosomes, and also increasing superficial PD-L1 ( 39 ). So the phenotype transition driven by intra-arterial chemotherapy could also enhance the efficacy of anti-PD therapies.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of intra-arterial chemotherapy with sequential anti-PD-1 antibody in unresectable gastric cancer: A retrospective real-world study

Xiang

Guo²,

Li³

et al. 2023

Front. Oncol.

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BackgroundThe prognosis of unresectable gastric cancer is poor, while the efficacy of anti-PD antibodies has not been evaluated.MethodsPatients with unresectable gastric cancer who received intra-arterial chemotherapy (IAC) with sequential anti-PD-1 antibody as induction therapy in Jinling Hospital were retrospectively analyzed. The primary outcome is R0 resection rate. The secondary outcomes include safety, conversion surgery rate, overall survival (OS) and progression free survival (PFS) after postoperative IAC and anti-PD-1 treatments. Meanwhile, Tumor immunity in the microenvironment (TIME) before and after IAC was comprehensively dissected with multiplex immunofluorescence in order to detect possible mechanisms favoring anti-PD-1 treatment response.ResultsBetween May 2019 and October 2020, 36 patients received at least one cycle of IAC with sequential anti-PD-1 antibody in our institution. The objective response was achieved in 28 patients (77.8%). Thirty patients (83.3%) successfully underwent conversion surgery, among which R0 resection was managed in 25/30 patients, and 23.3% (7/30) was assessed as pathological complete remission. During the median follow-up period of 19.7 months, patients who underwent R0 resection displayed superior OS (HR 0.14 [95% CI 0.04-0.50], P < 0.0001) and PFS (HR 0.11 [0.03-0.44], P < 0.0001) than those who did not. Grade 3 adverse events (AEs) were only encountered in 19.4% patients, no grade 4 AEs observed. In TIME analysis, the number of tertiary lymphoid structures (TLSs) (P = 0.004) were greatly induced by IAC, as well as CD8+ T cells (P = 0.011) and PD-1+ cells (P = 0.025). Meanwhile, Tumor associated macrophages shifted towards anti-tumor M1-like subtypes, with CD68+CD163+ M2-like subpopulation significantly decreased (P = 0.04).ConclusionPreoperative IAC with sequential anti-PD-1 antibody exhibited promising clinical benefit for unresectable gastric cancer with remarkable conversion rate and R0 resection rate, and also prolonged survival as postoperative regimen. TIME transformation induced by ICA might mediate the additive effect with the immune checkpoint inhibitor.

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“…Although there was no statistical difference in the expression of TAM (M2) between the composite score subgroups, the in ltration by TAM (M2) was high and statistically signi cant in the high-risk IRGPI or m 6 A risk score subgroups, which is consistent with the results of our survival analysis. In addition, tumor drug resistance is the main cause of chemotherapy failure, and studies have shown that TAMs are closely related to the drug resistance of tumors [39,40]. Chimeric antigen receptor macrophages (CAR-M) have been demonstrated to enter solid tumors and survive in the tumor environment, triggering long-lasting adaptive immune responses [4,37].…”

Section: Discussionmentioning

confidence: 99%

A composite score based on immune-related gene prognostic index and m6A risk score of head and neck squamous cell carcinoma

Yang

Lin

Cai

et al. 2022

Preprint

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Background: Immunotherapy has been demonstrated favorable in head and neck squamous cell carcinoma (HNSCC). Studies indicated that immune-related gene prognostic index (IRGPI) was a robust signature, and N6-methyladenosine (m6A) methylation had a significant impact on the tumor immune microenvironment (TIME) and immunotherapy of HNSCC. Thus, combining IRGPI with m6A status should offer a better predictive power for immune responses.Methods: HNSCC samples from The Cancer Genome Atlas (TCGA, n=498) and Gene Expression Omnibus database (GSE65858, n = 270) were used in this study. Cox regression analysis was used to construct the IRGPI through immune-related hub genes which were identified by weighted gene co-expression network analysis (WGCNA). The m6A risk score was constructed by least absolute shrinkage and selection operator regression analysis. Principal component analysis was used to construct a composite score, and systematically correlate subgroups according to TIME cell-infiltrating characteristics.Results: A composite score was determined based on IRGPI and m6A risk score. HNSCC patients in the TCGA were divided into four subgroups：A (IRGPI-High&m6A-risk-High, n=127), B (IRGPI-High&m6A-risk-Low, n=99), C (IRGPI-Low&m6A-risk-High, n=99) and D (IRGPI-Low&m6A-risk-Low, n=128), and overall survival (OS) was significantly different between subgroups (P < 0.001). The characteristics of TIME cell infiltration in the four subgroups were significantly different in subgroups (P < 0.05). The ROC curves show the predictive value of composite score for OS was superior to any other scores.Conclusions: The composite score is a promising prognostic signature which might distinguish immune and molecular characteristics, predict prognosis, and guide more effective immunotherapeutic strategies for HNSCC.

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Tumor-Associated Macrophages Regulate PD-1/PD-L1 Immunosuppression

Cited by 133 publications

References 134 publications

Construction of a tumor immune infiltration macrophage signature for predicting prognosis and immunotherapy response in liver cancer

Construction of a tumor immune infiltration macrophage signature for predicting prognosis and immunotherapy response in liver cancer

Efficacy of intra-arterial chemotherapy with sequential anti-PD-1 antibody in unresectable gastric cancer: A retrospective real-world study

A composite score based on immune-related gene prognostic index and m6A risk score of head and neck squamous cell carcinoma

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