Prognostic Impact of Tumor-Associated Macrophages on Long-Term Oncologic Outcomes in Colorectal Cancer.
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ABSTRACT:
SUBMITTER: Shin HC
PROVIDER: S-EPMC8618174 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThis study aimed to explore the prognostic significance of tumor-associated macrophage (TAM) infiltration in colorectal cancer (CRC) patients.MethodsTissue microarray and immunohistochemistry were used to detect the infiltration of CD163+ TAMs in 209 CRC samples, and the Kaplan-Meier method was used for survival analysis. Cox proportional hazards analysis was used for univariate analysis and multivariate analysis of clinically relevant confounders.ResultsThe samples were divided into low-level (n = 105) and high-level infiltration groups (n = 104) by the median number of CD163+ TAMs detected. The overall survival (OS) and disease-free survival (DFS) of CRC patients in the low-level CD163+ TAM infiltration group were longer than those in the high-level CD163+ TAM infiltration group (P < 0.001). Infiltration of CD163+ TAMs in CRC tissues was a negative prognostic factor for CRC patients. Risks of death and disease recurrence for CRC patients in the low-level CD163+ TAM infiltration group were lower than those in the high-level CD163+ TAM infiltration group (HROS = 0.183, 95% CI 0.052-0.647, P = 0.008; HRDFS = 0.191, 95% CI 0.078-0.470, P = 0.000).ConclusionsThe infiltration of CD163+ TAMs in CRC tissue is an independent adverse factor for the prognosis of CRC patients. High-level infiltration of CD163+ TAMs is associated with shorter OS and DFS.
| S-EPMC8229299 | biostudies-literature
Project description:ObjectiveTo evaluate the recurrence and functional outcomes in a primarily hereditary cohort of patients undergoing partial adrenalectomy for pheochromocytoma.MethodsA retrospective review from a prospectively managed database of patients undergoing partial adrenalectomy from 1995 to 2018 at the National Cancer Institute was performed. Local recurrence was defined as imaging evidence of a recurrent or de novo lesion on the operative side. Steroid dependency was defined as requiring daily steroid replacement at time of last follow-up.ResultsOne hundred and twenty-four partial adrenalectomies, removing 162 tumors, were performed in 107 patients. Most patients had a known hereditary predisposition to develop bilateral, multifocal, and recurrent pheochromocytoma. Median tumor size was 2 cm (interquartile range (IQR) 1.5-2.8). Median follow-up was 60 months (IQR 13-131). Local recurrence occurred in 17 patients (15.8%) and were managed with active surveillance or surgery. A single patient (1/106, 0.9%) developed metastatic spread of pheochromocytoma approximately 14 years after his first of 2 partial adrenalectomies and remains alive under active surveillance. Median time to recurrence was 71 months (IQR 26-127) with 10 patients (9.3%) requiring daily steroid replacement at time of last follow-up.ConclusionPartial adrenalectomy offers excellent oncologic and functional outcomes, sparing most patients from lifelong steroid replacement therapy. Recurrences can be easily managed with repeat surgery or active surveillance via functional work-up and imaging. Partial adrenalectomy remains the recommended surgical management for patients pre-disposed to development of bilateral, multifocal and recurrent pheochromocytoma.
| S-EPMC7255958 | biostudies-literature
Project description:BackgroundHaemoptysis is a challenging symptom that can be associated with potentially life-threatening medical conditions. Follow-up is key in these patients to promptly detect new or misdiagnosed pathologic findings. Few prospective studies have evaluated long-term prognostic outcomes in patients with haemoptysis. Furthermore, the role played by antiplatelet and anticoagulant drugs on mortality and recurrence rates is unclear. The aim of this study was to assess mortality after 18 months of follow-up. Furthermore, the incidence of recurrence and the risk factors for recurrence and death were evaluated (including the role played by anticoagulant and antiplatelet drugs).MethodsObservational, prospective, multicentre, Italian study.Results451/606 (74.4%) recruited patients with haemoptysis completed the 18 months follow-up. 22/604 (3.6%) diagnoses changed from baseline to the end of the follow-up. 83/604 (13.7%) patients died. In 52/83 (62.7%) patients, death was the outcome of the disease which caused haemoptysis at baseline. Only the diagnosis of lung neoplasm was associated with death (OR (95%CI): 38.2 (4.2-347.5); p-value: 0.0001). 166 recurrences were recorded in 103/604 (17%) patients. The diagnosis of bronchiectasis was significantly associated with the occurrence of a recurrence (OR (95% CI): 2.6 (1.5-4.3)); p-value < 0.0001). Anticoagulant, antiaggregant, and anticoagulant plus antiaggregant drugs were not associated with an increased risk of death and recurrence.ConclusionsOur study showed a low mortality rate in patients with haemoptysis followed-up for 18 months. Pulmonary malignancy was the main aetiology and the main predictor of death, whereas bronchiectasis was the most frequent diagnosis associated with recurrence. Antiplatelet and/or anticoagulant therapy did not change the risk of death or recurrence. Follow-up is recommended in patients initially diagnosed with lower airways infections and idiopathic bleeding.Trial registrationNCT02045394.
| S-EPMC8336236 | biostudies-literature
Project description:Tumor microenvironment and immune escape affect pathogenesis and survival in classical Hodgkin lymphoma (cHL). While tumor-associated macrophage (TAM) content has been associated with poor outcomes, macrophage-derived determinants with clinical impact have remained undefined. Here, we have used multiplex immunohistochemistry and digital image analysis to characterize TAM immunophenotypes with regard to expression of checkpoint molecules programmed cell death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO-1) from the diagnostic tumor tissue samples of 130 cHL patients, and correlated the findings with clinical characteristics and survival. We show that a large proportion of TAMs express PD-L1 (CD68+, median 32%; M2 type CD163+, median 22%), whereas the proportion of TAMs expressing IDO-1 is lower (CD68+, median 5.5%; CD163+, median 1.4%). A high proportion of PD-L1 and IDO-1 expressing TAMs from all TAMs (CD68+), or from CD163+ TAMs, is associated with inferior outcome. In multivariate analysis with age and stage, high proportions of PD-L1+ and IDO-1+ TAMs remain independent prognostic factors for freedom from treatment failure (PD-L1+CD68+/CD68+, HR = 2.63, 95% CI 1.17-5.88, p = 0.019; IDO-1+CD68+/CD68+, HR = 2.48, 95% CI 1.03-5.95, p = 0.042). In contrast, proportions of PD-L1+ tumor cells, all TAMs or PD-L1- and IDO-1- TAMs are not associated with outcome. The findings implicate that adverse prognostic impact of TAMs is checkpoint-dependent in cHL.
| S-EPMC7225916 | biostudies-literature
Project description:BackgroundThe tumor microenvironment plays a major tumor-supportive role in glioma. In particular, tumor-associated macrophages (TAMs), which can make up to one-third of the tumor mass, actively support tumor growth, invasion, and angiogenesis. Predominantly alternatively activated (M2-polarized) TAMs are found in late-stage glioma in both human and mouse tumors, as well as in relapse samples from patients. However, whether tumor-educated M2 TAMs can actively contribute to the emergence and growth of relapse is currently debated.MethodsTo investigate whether tumor-educated stromal cells remaining in the brain after surgical removal of the primary tumor can be long-lived and retain their tumor-supporting function, we developed a transplantation mouse model and performed lineage-tracing.ResultsWe discovered that macrophages can survive transplantation and stay present in the tumor much longer than previously suggested, while sustaining an M2-polarized protumorigenic phenotype. Transplanted tumors showed a more aggressive growth and faster polarization of the TAMs toward an M2 phenotype compared with primary tumors, a process dependent on the presence of few cotransplanted macrophages.ConclusionsOverall, we propose a new way for tumor-educated TAMs to contribute to glioma aggressiveness by long survival and stable protumorigenic features. These properties could have a relapse-supporting effect.
| S-EPMC7649962 | biostudies-literature
Project description:Tumor-associated macrophages (TAM) play a controversial role in epithelial-mesenchymal transition (EMT) and prognosis of colorectal cancer (CRC). In particular, the microlocalization, polarization and prognostic impact of TAM in the immediate environment of invading CRC cells has not yet been established. To address this clinically relevant question, intraepithelial (iCD68) and stromal macrophages (sCD68), M1-macrophages (iNOS), M2-macrophages (CD163), cytokeratin-positive cancer cells (tumor buds) and expression of the anti-phagocytic marker CD47 were investigated in primary tumors of 205 well-characterized CRC patients. Cell-to-cell contacts between tumor buds and TAM were detected using high-resolution digital scans. The composition of the tumor microenvironment was analyzed with clinicopathological and molecular features. High CD68 counts predicted long term overall survival independent of microlocalization (iCD68 p=0.0016; sCD68 p=0.03), pT, pN, pM and post-operative therapy. CD68 infiltration correlated with significantly less tumor budding (iCD68 p=0.0066; sCD68 p=0.0091) and absence of lymph node metastasis (sCD68 p=0.0286). Cell-to-cell contact of sCD68 and invading cancer cells was frequent and ameliorated the detrimental prognostic effect of the tumor budding phenotype. Subgroup analysis identified long-term survival with CD47 loss and predominance of CD163+ M2 macrophages (p = 0.0366). CD163+ macrophages represented 40% of the total population, and positively correlated with total CD68 macrophage numbers (r[CD68/CD163] = 0.32; p = 0.0001). Strong CD163 infiltration predicted lower tumor grade (p = 0.0026) and less lymph node metastasis (p = 0.0056). This study provides direct morphological evidence of an interaction between TAM and infiltrating cancer cells. The prognostic impact of TAM is modulated by phenotype, microlocalization and the expression of anti-phagocytic markers in CRC.
| S-EPMC4839334 | biostudies-literature
Project description:BackgroundClinical evidence has proved that enhanced recovery after surgery (ERAS) can improve short-term clinical outcomes after various types of surgeries, but the long-term benefits have not yet been examined, especially with respect to cancer surgeries. Therefore, a systematic review of the current evidence was conducted.MethodsThe Pubmed, Cochrane Library, Embase, and Web of Science databases were searched using the following key words as search terms: "ERAS" or "enhanced recovery" or "fast track", "oncologic outcome", "recurrence", "metastasis", "long-term outcomes", "survival", and "cancer surgery". The articles were screened using the inclusion and exclusion criteria, and the data from the included studies were extracted and analyzed.ResultsA total of twenty-six articles were included in this review. Eighteen articles compared ERAS and conventional care, of which, 12 studies reported long-term overall survival (OS), and only 4 found the improvement by ERAS. Four studies reported disease-free survival (DFS), and only 1 found the improvement by ERAS. Five studies reported the outcomes of return to intended oncologic treatment after surgery (RIOT), and 4 found improvements in the ERAS group. Seven studies compared high adherence to ERAS with low adherence, of which, 6 reported the long-term OS, and 3 showed improvements by high adherence. One study reported high adherence could reduce the interval from surgery to RIOT. Four studies reported the effect of altering one single item within the ERAS protocol, but the results of 2 studies were controversial regarding the long-term OS between laparoscopic and open surgery, and 1 study showed improvements in OS with restrictive fluid therapy.ConclusionsThe use of ERAS in cancer surgeries can improve the on-time initiation and completion of adjuvant chemotherapy after surgery, and the high adherence to ERAS can lead to better outcomes than low adherence. Based on the current evidence, it is difficult to determine whether the ERAS protocol is associated with long-term overall survival or cancer-specific survival.
| S-EPMC8243430 | biostudies-literature
Project description:Programmed cell death-ligand 1 (PD-L1) on tumor cells can be degraded to soluble form (sPD-L1) and enter circulation, however, the clinical significances of sPD-L1 in peripheral blood remains to be elucidated in non-small-cell lung cancer (NSCLC). We monitored plasma sPD-L1 levels during perioperative periods and evaluated PD-L1-positive cells in tumor tissues in patients with operable NSCLC. Then the correlation between preoperative plasma sPD-L1 levels and relapse-free survival (RFS) was analyzed retrospectively. In patients who underwent radical surgery (n = 61), plasma sPD-L1 levels (median; 63.5 pg/mL) significantly increased 1 month after surgery (72.2 pg/mL, P < 0.001). The combined score of PD-L1-positive cells including tumor cells and tumor-associated macrophages (TAMs) was significantly associated with preoperative plasma sPD-L1 levels. In patients with high levels of preoperative plasma sPD-L1, the probability of 5-year RFS was significantly poor for patients with low PD-L1 expression intensity of tumor cells (tcPD-L1) compared with those with high tcPD-L1 (33.3% vs. 87.5%, respectively, P = 0.016; 95% CI, 0.013-0.964). In former group, PD-L1-positive TAMs were markedly infiltrating compared with those from latter group (246.4 vs. 76.6 counts/mm2, respectively, P = 0.003). In NSCLC, plasma sPD-L1 can reflect the accumulation of PD-L1-posotive TAMs, not just PD-L1-positive tumor cells. In patients with high levels of preoperative plasma sPD-L1, the prognoses after surgery depends on which PD-L1-positive cells, tumor cells or TAMs, are the primary source of the sPD-L1. Thus, measuring both plasma sPD-L1 levels and PD-L1 expression status of tumor cells and TAMs is of benefit for assessment of postoperative prognosis in operable NSCLC.
| S-EPMC10576714 | biostudies-literature
Project description:BACKGROUND AND AIMS:Endoscopic resection (ER) for submucosal invasive colorectal cancer (T1 CRC) can be grouped as curative ER (C-ER) and non-curative ER (NC-ER). Little is known about the long-term outcomes of patients in these two groups. Therefore, we have evaluated the long-term outcomes in endoscopically resected T1 CRC patients in C-ER and NC-ER groups. METHODS:We conducted a retrospective study on 220 patients with T1 CRC treated with ER from January 2007 to December 2017. First, we investigated the long-term outcomes (5-year overall survival [OS] and recurrence-free survival [RFS]) in the C-ER group (n = 49). In the NC-ER group (n = 171), we compared long-term outcomes between patients who underwent additional surgical resection (ASR) (n = 117) and those who did not (surveillance-only, n = 54). RESULTS:T1 CRC patients in the C-ER and NC-ER groups had a median follow-up of 44 (interquartile range 32-69) months. There was no risk of tumor recurrence and cancer-related deaths in patients with C-ER. In the NC-ER group, the 5-year OS rates were 75.3% and 92.6% in the surveillance-only and ASR subgroups, respectively. The hazard ratio (HR) for ASR in NC-ER vs. surveillance-only in NC-ER was statistically insignificant. However, RFS rates were significantly different between the ASR (97.2%) and surveillance-only (84.0%) subgroups. Multivariate analysis indicated a submucosal invasion depth (SID) of >2500 µm and margin positivity to be associated with recurrence. CONCLUSIONS:The surveillance-only approach can be considered as an alternative surgical option for T1 CRCs in selected patients undergoing NC-ER.
| S-EPMC7464364 | biostudies-literature
Project description:Although macrophages are important players in the injury/repair processes in animal models of acute kidney injury (AKI), their roles in human AKI remains uncertain owing to a paucity of human biopsy studies. We investigated the role of macrophages in 72 cases of biopsy-proven acute tubular necrosis (ATN) and six cases of healthy kidney. Macrophages were identified by CD68 and CD163 immunohistochemistry and analyzed for their effect on renal outcomes. CD163+ M2 macrophages outnumbered CD68+ cells in the healthy kidneys, suggesting that CD163+ macrophages are resident macrophages. The infiltration of both subtypes of macrophages increased significantly in ATN. The density of the CD68+ macrophages was significantly higher in advanced-stage AKI, whereas CD163+ M2 macrophages was not. Eighty percent of patients exhibited renal functional recovery during follow-up. Older age and a higher density of CD163+ macrophages predicted non-recovery, whereas the AKI stage, tubular injury score, and density of CD68+ cells did not. The density of CD163+ M2 macrophages was an independent predictor of low eGFR at 3 months in advanced-stage AKI. This is the first human study demonstrating the possible role of macrophages in the injury and repair phases of AKI.
| S-EPMC7005727 | biostudies-literature