The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time

Ma, Junliang; Liu, Lunxu; Che, Guowei; Yu, Na; Dai, Fuqiang; You, Zongbing

doi:10.1186/1471-2407-10-112

Cited by 375 publications

(372 citation statements)

References 18 publications

(26 reference statements)

Supporting

Mentioning

347

Contrasting

Unclassified

Order By: Relevance

“…34 The respective LIP indices in the macrophage subsets, CD11b 1 CD163 1 and HLA-DR 1 CD163 1 , were significantly higher in patients with ACLF-MOF, as compared to other groups. The cell numbers were not significantly altered, suggesting a probable classical activation of macrophage in iron production, storage as LIP, and release in ACLF patients.…”

Section: Discussionmentioning

confidence: 81%

Dysregulated iron homeostasis is strongly associated with multiorgan failure and early mortality in acute‐on‐chronic liver failure

et al. 2015

View full text Add to dashboard Cite

Acute-on-chronic liver failure (ACLF) is an ailment with high incidence of multiorgan failure (MOF) and consequent mortality. Dysregulated iron homeostasis and macrophage dysfunction are linked to increased incidence of MOF. We investigated whether a panel of circulating iron-regulating proteins are associated with development of MOF and can predict 15-or 30-day mortality in ACLF patients. One hundred twenty patients with ACLF, 20 patients with compensated cirrhosis, and 20 healthy controls were studied. Relative protein expression profiling was performed in the derivative cohort and confirmed in the validation cohort. A panel of iron regulators and indices were determined. Multiparametric flow cytometry for quantitation of labile iron pool (LIP) was performed. Validation studies confirmed lower serum transferrin (Tf) and ceruloplasmin levels in ACLF and ACLF-MOF, compared to patients with cirrhosis and controls (P < 0.01). Serum iron and ferritin levels were markedly elevated (P < 0.001; P < 0.05) and hepcidin levels were lower (P < 0.001) in ACLF patients with MOF than those without and other groups (P < 0.001). Percentage Tf saturation (%SAT) was higher in ACLF-MOF (39.2%; P < 0.001) and correlated with poor outcome (hazard ratio: 6.970; P < 0.01). Intracellular LIP indices were significantly elevated in the subsets of circulating macrophages in ACLF-MOF, compared to other groups (P < 0.01). Whereas expression of iron-regulatory genes was markedly down-regulated, genes related to endoplasmic reticulum stress, apoptosis, and inflammation were up-regulated in ACLF patients, compared to patients with cirrhosis. Severe dysregulation of autophagy mechanisms was also observed in the former. Conclusions: Iron metabolism and transport are severely deranged in ACLF patients and more so in those with MOF. %SAT, circulating hepcidin, and LIP in macrophages correlate with disease severity and %SAT could be used for early prognostication in ACLF patients. (HEPATOLOGY 2015;61:1306-1320

show abstract

Section: Discussionmentioning

confidence: 81%

Dysregulated iron homeostasis is strongly associated with multiorgan failure and early mortality in acute‐on‐chronic liver failure

et al. 2015

View full text Add to dashboard Cite

show abstract

“…This may explain the inconsistency that macrophages in tumor islets are stronger predictors for survival in early-stage NSCLC, [20][21][22] whereas those in the …”

Section: Discussionmentioning

confidence: 99%

“…19 TAMs have since been shown to differentially correlate with survival of NSCLC patients according to their microanatomic localization. As such, although stromal TAMs are frequently negatively associated with patient survival, 20,21 tumor islet TAMs are consistently positively correlated with patient survival. 21,22 Nevertheless, the fact that the majority of TAMs localize in the tumor stroma 2 and express protumor M2 markers 20 still supports a protumor role of TAMs in most NSCLC patients, as observed in earlier studies.…”

Section: Introductionmentioning

confidence: 99%

“…As such, although stromal TAMs are frequently negatively associated with patient survival, 20,21 tumor islet TAMs are consistently positively correlated with patient survival. 21,22 Nevertheless, the fact that the majority of TAMs localize in the tumor stroma 2 and express protumor M2 markers 20 still supports a protumor role of TAMs in most NSCLC patients, as observed in earlier studies. 18,19 Furthermore, this is supported by a recent report from Ohtaki et al, 23 who demonstrated an association between CD204-positive stromal macrophages and poor outcomes, indicating the protumor effect of stromal macrophages.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tumor‐associated macrophages correlate with response to epidermal growth factor receptor‐tyrosine kinase inhibitors in advanced non‐small cell lung cancer

Chung

Lee

Wang

et al. 2012

Intl Journal of Cancer

View full text Add to dashboard Cite

Our study investigated whether tumor-associated macrophages (TAMs) in advanced non-small cell lung cancer (NSCLC) are related to treatment response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and may be a predictor of survival. Of 206 advanced NSCLC patients treated (first-line) with an EGFR-TKI at the study hospital from 2006 to 2009, 107 with adequate specimens for assessing CD68 immunohistochemistry as a marker of TAMs were assessed. After EGFR-TKI treatment, response was observed in 55 (51%) patients, and the median follow-up period was 13.5 months. Most TAMs were located in the tumor stroma (>95%) and positively costained with the M2 marker CD163. TAM counts were significantly higher in patients with progressive disease than in those without (p < 0.0001), a trend that remained in patients with known EGFR mutation status (n 5 59) and those with wild-type EGFR (n 5 20). High TAM counts, among other factors (e.g., wild-type EGFR), were significantly related to poor progression-free survival (PFS) and overall survival (OS) (all p < 0.0001 for TAMs). Multivariate Cox analyses showed that high TAM counts and EGFR mutations were both independent factors associated with PFS [odds ratio (OR), 8.0; 95% confidence interval (CI), 2.87-22.4; p 5 0.0001 and OR, 0.03; 95% CI, 0.003-0.31; p 5 0.003, respectively] and OS (OR, 2.641; 95% CI, 1.08-6.5; p 5 0.03 and OR, 0.14; 95% CI, 0.03-0.56; p 5 0.006, respectively). TAMs are related to treatment response irrespective of EGFR mutation and can independently predict survival in advanced NSCLC treated with an EGFR-TKI.

show abstract

“…20 Other studies also showed a positive relationship between M1 infiltration and survival. [36][37][38][39][40] Notably, HPV-induced vulvar carcinomas are known for their good overall prognosis and survival rate of approximately 80%. 41,42 In the current study, the increased presence of single CD141 cells, representative for M1 macrophages, was related to a decreased RFS but so was the number of all intraepithelial CD141 cells, comprising both M1 and M2 macrophages.…”

Section: Discussionmentioning

confidence: 99%

Intraepithelial macrophage infiltration is related to a high number of regulatory T cells and promotes a progressive course of HPV‐induced vulvar neoplasia

Esch

Poelgeest

Trimbos

et al. 2014

Intl Journal of Cancer

View full text Add to dashboard Cite

Human papilloma virus (HPV)-induced usual-type vulvar intraepithelial neoplasia (uVIN) is infiltrated by myeloid cells but the type and role of these cells is unclear. We used triple immunofluorescent confocal microscopy to locate, identify and quantify myeloid cells based on their staining pattern for CD14, CD33 and CD163 in a cohort of 43 primary and 20 recurrent uVIN lesions, 21 carcinomas and 26 normal vulvar tissues. The progressive course of uVIN is characterized by an increase in both intraepithelial and stromal mature M1 and M2 macrophages. While the M2 macrophages outnumber M1 macrophages in healthy controls and uVIN, they are matched in number by M1 macrophages in cancer. Importantly, uVIN patients with a dense intraepithelial infiltration with mature CD141 macrophages (irrespective of M1 or M2 type) displayed approximately a six times higher risk to develop a recurrence and a high number of these cells constituted an independent prognostic factor for recurrence. In addition, a dense intraepithelial CD141 cell infiltration was associated with high numbers of intraepithelial CD41 Tregs and low numbers of stromal CD81TIM31 T cells. Patients with low numbers of intraepithelial CD141 cells and high numbers of stromal CD81TIM31 cells showed the best recurrence-free survival. These data clearly show the importance of the local immune response in HPV-induced vulvar neoplasia and may be of help in predicting the prognosis of patients or their response to immunotherapy.Usual-type vulvar intraepithelial neoplasia (uVIN) lesions are caused by a persistent high-risk human papilloma virus (HPV) infection (mainly HPV 16) and are characterized by high recurrences, a low spontaneous regression rate of 1.5% and a malignant potential of 3-4% in treated patients. [1][2][3] Treatment of uVIN lesions is indispensable since 80% of patients suffer from symptoms as pruritis and pain. 2-4 Conventional treatment consistent of potential disfiguring surgical interventions is associated with psychosexual problems and is increasingly replaced by either standardized immunotherapy with imiquimod or immunotherapy in experimental setting by therapeutic vaccination or photodynamic therapy, with promising clinical successes. [2][3][4][5][6][7][8] The incidence of hrHPV-induced dysplasia is increased in immunocompromised patients highlighting the essential role of the immune system in viral clearance. 9,10 Spontaneous regression of HPV is associated with systemic HPV-specific CD41 and CD81 immune responses, however in most of the patients with uVIN these T cell responses are either weak or absent. 11,12 In addition, the local innate immune cell environment is known to influence innate and adaptive immune responses in tumors. 13,14 Monocytes are innate immune cells which can differentiate into dendritic cells (DCs) or macrophages in response to local factors. 13 DCs process and present antigens to T cells, stimulate cytotoxicity of NK cells and initiate the adaptive immune response. 15 Studies of the microenvironment in uVIN revealed that ...

show abstract

The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time

Cited by 375 publications

References 18 publications

Dysregulated iron homeostasis is strongly associated with multiorgan failure and early mortality in acute‐on‐chronic liver failure

Dysregulated iron homeostasis is strongly associated with multiorgan failure and early mortality in acute‐on‐chronic liver failure

Tumor‐associated macrophages correlate with response to epidermal growth factor receptor‐tyrosine kinase inhibitors in advanced non‐small cell lung cancer

Intraepithelial macrophage infiltration is related to a high number of regulatory T cells and promotes a progressive course of HPV‐induced vulvar neoplasia

Contact Info

Product

Resources

About