Prognostic impact of preoperative monocyte counts in patients with resected lung adenocarcinoma

Kumagai, Shogo; Marumo, Satoshi; Tanaka, Shōji; Sakuramoto, Minoru; Hirai, Tatsuya; Nishimura, Takafumi; Arima, Nobuyoshi; Fukui, Motonari; Huang, Cheng‐Long

doi:10.1016/j.lungcan.2014.06.015

Cited by 56 publications

(58 citation statements)

References 32 publications

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“…Supportive macrophages or nurse-like cells have been established as important constituents of this microenvironment, favoring CLL cell viability and providing protection from numerous CLL directed therapies [3, 5, 6, 21]. In other malignancies, an elevated AMC is associated with higher density of tumor associated macrophages [8]. Thus, in CLL, a higher AMC could reflect a higher level of monocytes and macrophages in the tumor microenvironment, which as a protective feature for CLL cells would confer inferior outcomes for patients.…”

Section: Discussionmentioning

confidence: 99%

Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi‐institutional study

et al. 2016

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Background Monocyte-derived cells, constituents of the cancer microenvironment, support chronic lymphocytic leukemia (CLL) cell survival in vitro via direct cell-cell interaction and secreted factors. We hypothesized that circulating absolute monocyte count (AMC) reflects the monocyte-derived cells in the microenvironment, and that higher AMC is associated with increased CLL cell survival in vivo and thus inferior CLL patient outcomes. Methods We assessed the extent to which AMC at diagnosis of CLL is correlated with clinical outcomes, and whether this information adds to currently used prognostic markers. We evaluated AMC, clinically used prognostic markers, and time to event data from 1,168 CLL patients followed at the Mayo Clinic, the Duke University Medical Center, and the Durham VA Medical Center. Results Elevated AMC was significantly associated with inferior clinical outcomes, including time to first therapy (TTT) and overall survival (OS). AMC combined with established clinical and molecular prognostic markers significantly improved risk-stratification of CLL patients for TTT. Conclusions Elevated AMC at diagnosis is associated with inferior CLL patient outcomes and accelerated disease progression. Monocyte-derived cells in the CLL microenvironment promote CLL cell survival and proliferation. Together, these findings suggest that monocytes and monocyte-derived cells are rational therapeutic targets in CLL.

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Section: Discussionmentioning

confidence: 99%

Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi‐institutional study

et al. 2016

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“…Absolute lymphocyte count was proven to be an independent prognostic factor in bladder cancer, melanoma and extranodal natural killer/T-cell lymphoma 8-10. Elevated monocyte count has been demonstrated to predict poor prognosis in mantle cell lymphoma, colorectal cancer and lung adenocarcinoma 11-13. Lymphocyte-to-monocyte ratio (LMR) has been shown to be a prognostic factor for patients with hepatocellular carcinoma and endometrial cancer 14, 15.…”

Section: Introductionmentioning

confidence: 99%

Peripheral blood lymphocyte-to-monocyte ratio as a prognostic factor in advanced epithelial ovarian cancer: a multicenter retrospective study

Zhu¹,

Liu²,

Wang³

et al. 2017

J. Cancer

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The lymphocyte-to-monocyte ratio (LMR), as a surrogate marker of systemic inflammation, has been found to be a novel prognostic indicator in various malignancies. Data from 672 advanced epithelial ovarian cancer (EOC) patients treated with neoadjuvant chemotherapy (NAC) followed by debulking surgery were analyzed, and the prognostic value of LMR were evaluated. The optimal cutoff point of LMR in prediction of survival was defined as 3.45 through receiver operating characteristics curve analysis. Patients with low LMR (≤3.45) at diagnosis tended to have more adverse clinical features, such as higher histological grade, chemotherapy resistance, and residual tumor >1cm after debulking surgery. No significant correlation was found between LMR level and age and histological type. Moreover, after NAC, the complete remission (CR) rate for the low-LMR group was lower than those for the high-LMR group (P<0.05). Patients with low LMR had poorer progression-free survival (PFS; P<0.001) and overall survival (OS; P<0.001). Multivariate analysis revealed that low LMR was an independent adverse predictor for PFS and OS. Results indicated that low LMR at diagnosis is a novel independent prognostic factor for advanced EOC. However, prospective study is needed to validate this prognostic factor and biological studies should further investigate the mechanisms underlying the correlation between low LMR and poor prognosis in advanced EOC.

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“…It has been observed that levels of circulating inflammatory monocytes (IM) negatively correlate with prognosis across several types of cancers [6, 11–15, 34–36]. However, it is unclear how common cancer modalities such as radiotherapy (RT) impact the number of circulating IM.…”

Section: Resultsmentioning

confidence: 99%

“…This is important, as the level of monocytes in preoperative cancer patients’ complete blood counts has been shown to correlate with poor prognosis across several tumor types [6, 11–15]. Due to the predominately restricted expression of CCR2 on IM in the blood, we suggest that CCR2+ IM could serve as a biomarker to identify candidates for CCR2/CCR5 blockade post-RT.…”

Section: Discussionmentioning

confidence: 95%

“…To this end, preclinical studies that broadly target the intratumoral myeloid cells have augmented the anti-tumor responses in some RT models [4, 7–10]. Furthermore, it has been recently established that high preoperative circulating monocyte levels negatively correlate with prognosis across many types of solid tumor malignancies [6, 11–15]. These findings have led to successful clinical trials in which therapies that block the infiltration of inflammatory monocytes (IM) into tumors have shown unanticipated promise [16].…”

Section: Introductionmentioning

confidence: 99%

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Increasing the efficacy of radiotherapy by modulating the CCR2/CCR5 chemokine axes

et al. 2016

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Although radiotherapy (RT) is widely used to control tumor growth across many cancer types, there is a relatively high incidence of RT failure exhibited by tumor recurrence, therefore a clear need exists to achieve improved effectiveness of RT. The RT-elicited immune response largely impacts the efficacy of RT and includes immune cells that kill tumor cells, but also immunosuppressive cells, which dampen anti-tumor immunity. Using murine models in which syngeneic tumor cell lines (Colon38, Glioma261, Line1) are grown intramuscularly and treated with 15 Gy local RT, we assessed the effects of RT on both the systemic and intratumoral immune response. Here we demonstrate that RT stimulates increased production of two chemokines, CCL2 and CCL5, at the tumor site. Further, that this leads to increased CCR2+ CCR5+ monocytes in circulation and subsequently alters the intratumoral immune infiltrate favoring the largely immunosuppressive CCR2+ CCR5+ monocytes. Importantly, a CCR2/CCR5 antagonist administered daily (15 mg/kg subcutaneously) starting two days prior to RT reduces both circulating and intratumoral monocytes resulting in increased efficacy of RT in radioresponsive tumors. Overall, these data have important implications for the mechanism of RT and present a means to improve RT efficacy across many cancer types.

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Prognostic impact of preoperative monocyte counts in patients with resected lung adenocarcinoma

Cited by 56 publications

References 32 publications

Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi‐institutional study

Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi‐institutional study

Peripheral blood lymphocyte-to-monocyte ratio as a prognostic factor in advanced epithelial ovarian cancer: a multicenter retrospective study

Increasing the efficacy of radiotherapy by modulating the CCR2/CCR5 chemokine axes

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