Postoperative serum interleukin-6 levels correlate with survival in stage I-III colorectal cancer

Feng, Shou-Han; Li, Zeshi; Liu, Mei; Ye, Qianwen; Xue, Tianhui; Yan, Bing

doi:10.1186/s12876-023-02800-9

Cited by 6 publications

(7 citation statements)

References 76 publications

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“…After postoperative tumor resection, plasma IL-6 was still induced prominently in the IgG2b, κ group. Escalation of circulating IL-6 levels has been previously reported to associate with systemic inflammation in cancer patients undergoing surgery 52 , thus facilitating EMT and BCSCs expansion 33 and contributing to progressive metastasis 53 . This was matched with increased distant metastasis after scramble and shMCT-1 groups underwent tumor resection (Figure 4 C).…”

Section: Resultsmentioning

confidence: 99%

Immunotherapeutic IL-6R and targeting the MCT-1/IL-6/CXCL7/PD-L1 circuit prevent relapse and metastasis of triple-negative breast cancer

Haq,

Yang,

Jin

et al. 2024

Theranostics

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Rationale: Multiple copies in T-cell malignancy 1 (MCT-1) is a prognostic biomarker for aggressive breast cancers. Overexpressed MCT-1 stimulates the IL-6/IL-6R/gp130/STAT3 axis, which promotes epithelial-to-mesenchymal transition and cancer stemness. Because cancer stemness largely contributes to the tumor metastasis and recurrence, we aimed to identify whether the blockade of MCT-1 and IL-6R can render these effects and to understand the underlying mechanisms that govern the process. Methods: We assessed primary tumor invasion, postsurgical local recurrence and distant metastasis in orthotopic syngeneic mice given the indicated immunotherapy and MCT-1 silencing (shMCT-1). Results: We found that shMCT-1 suppresses the transcriptomes of the inflammatory response and metastatic signaling in TNBC cells and inhibits tumor recurrence, metastasis and mortality in xenograft mice. IL-6R immunotherapy and shMCT-1 combined further decreased intratumoral M2 macrophages and T regulatory cells (Tregs) and avoided postsurgical TNBC expansion. shMCT-1 also enhances IL-6R-based immunotherapy effectively in preventing postsurgical TNBC metastasis, recurrence and mortality. Anti-IL-6R improved helper T, cytotoxic T and natural killer (NK) cells in the lymphatic system and decreased Tregs in the recurrent and metastatic tumors. Combined IL-6R and PD-L1 immunotherapies abridged TNBC cell stemness and M2 macrophage activity to a greater extent than monotherapy. Sequential immunotherapy of PD-L1 and IL-6R demonstrated the best survival outcome and lowest postoperative recurrence and metastasis compared with synchronized therapy, particularly in the shMCT-1 context. Multiple positive feedforward loops of the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 axis were identified in TNBC cells, which boosted metastatic niches and immunosuppressive microenvironments. Clinically, MCT-1 high /PD-L1 high /CXCL7 high and CXCL7 high /IL-6 high /IL-6R high expression patterns predict worse prognosis and poorer survival of breast cancer patients. Conclusion: Systemic targeting the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 interconnections enhances immune surveillance that inhibits the aggressiveness of TNBC.

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Section: Resultsmentioning

confidence: 99%

Immunotherapeutic IL-6R and targeting the MCT-1/IL-6/CXCL7/PD-L1 circuit prevent relapse and metastasis of triple-negative breast cancer

Haq,

Yang,

Jin

et al. 2024

Theranostics

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“…4,29 However, opposite results were reported for colorectal and breast cancers in early stages. 14,15 IL-6 immunoreactivity has been investigated in the cytoplasm of tumor cells in a large group of CRC patients (n = 160). 10 The IL-6-positive (IL-6 + ) tumor group has been associated with advanced tumor stage, lymph node metastasis, and vascular invasion and do not correlate with serum IL-6 levels.…”

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confidence: 99%

“…It is a pleiotropic cytokine with distinguished protumor functions stimulating tumor cell proliferation, angiogenesis, metastasis, and tumor progression 11–13 . However, several studies have reported the associations of IL-6 with good prognosis of cancers with different histologic origin 14,15 . Similarly, the higher mRNA expression of IL-6 in malignant melanoma has been reported to associate with longer survival of the patients in comparison with lower mRNA levels, while no such associations have been observed for head and neck squamous cell carcinoma (HNSCC), ovarian and breast cancers 16 …”

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confidence: 99%

“…Increased serum levels of IL-6 in CRC patients, studied before surgery, has been associated with disease development and poor prognosis 3,28 and with certain clinical parameters such as tumor invasion, advanced tumor stage, the risk of development of CRC 4,29 . However, opposite results were reported for colorectal and breast cancers in early stages 14,15 …”

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confidence: 99%

“… 4 , 29 However, opposite results were reported for colorectal and breast cancers in early stages. 14 , 15 …”

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confidence: 99%

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Interleukin-6-Positive Immune Cells as a Possible New Immunologic Marker Associated With the Colorectal Cancer Prognosis

Gulubova,

Chonov,

Aleksandrova

et al. 2024

Applied Immunohistochemistry &Amp; Molecular Morphology

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Chronic inflammation creates tumor microenvironment (TME) that facilitates colorectal cancer (CRC) cell proliferation, migration, metastasis, and tumor progression. Interleukin-6 (IL-6) is a proinflammatory cytokine with a pleiotropic effect on CRC development. We aimed to evaluate IL-6 expression in tumor cells and in immune cells in TME, to assess the serum level and IL6 -174 G/C genotype distribution and to correlate the results with selected morphologic and clinical parameters that may add useful information in understanding the mechanisms of human CRC progression. A total of 153 patients with CRC were recruited in the current study. We assessed the IL-6 serum concentration through the ELISA method, the expression of IL-6 in tumor and in immune cells by immunohistochemical and double immunofluorescence staining, the MSI status by immunоhistochemistry for 4 mismatch repair (MMR) proteins, and the genotype distributions for IL6 -174G/C (rs1800795) single-nucleotide polymorphism through PCR-RFLP method. Our results showed that serum IL-6 level were increased in CRC patients as compared with healthy controls (P<0.0001), and in patients with cancers with advanced histologic type (type IV). However, the higher concentration (above the median of 55.71 pg/mL) was with borderline association with longer survival of the patients after surgical therapy (P=0.055, Log rank test). We also found that IL-6+ immune cells prevailed in the invasive front (IF) of tumors compared with the tumor stroma (TS) (P<0.0001). More IL-6+ cells were recruited in the tumors with less advanced histologic type (I+II), with stronger inflammatory infiltrate in the IF, in early pTNM stages (I+II), without lymph node and distant metastases and the higher levels of IL-6+ cells, especially in the IF, were associated with longer survival (P=0.012). The results of our study suggest that although the serum levels of IL-6 are higher in CRC, the increased IL-6+ cells in tumor microenvironment, both in the invasive front and in tumor stroma, as well as the higher serum levels are associated with good prognostic variables and longer survival of the patients mainly in the early stages of CRC.

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Impact of severe postoperative complications on the prognosis of older patients with colorectal cancer: a two-center retrospective study

Matsubara,

Soga,

Ikeda

et al. 2024

BMC Gastroenterol

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Background The occurrence of postoperative complications may affect short-term outcomes and prognosis of patients with various malignancies. However, the prognostic impact of these complications in older patients with colorectal cancer (CRC) remains unclear. Therefore, this study aimed to investigate the impact of severe postoperative complications on the oncological outcomes of older (aged ≥ 80 years) and non-older (aged < 80 years) patients with CRC. Methods We retrospectively analyzed 760 patients with stage I–III CRC who underwent curative surgery in two institutions between 2013 and 2019. The patients were categorized into older (aged ≥ 80 years, 191 patients) and non-older (aged < 80 years, 569 patients) groups. Short- and long-term outcomes were compared between the two groups. Results The incidence of severe postoperative complications did not differ between the two groups (p = 0.981). Cancer-specific survival (CSS) was significantly worse in older patients with severe complications than in those without severe complications (p = 0.007); meanwhile, CSS did not differ between the non-older patients with severe complications and those without severe complications. Survival analysis revealed that the occurrence of severe postoperative complications was an independent prognostic factor for CSS in older patients (hazard ratio = 4.00, 95% confidence interval: 1.27–12.6, p = 0.017). Conclusion CRC surgery can be safely performed in older and non-older patients. Moreover, the occurrence of severe postoperative complications might more strongly affect the prognosis of older patients than that of non-older patients.

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Postoperative serum interleukin-6 levels correlate with survival in stage I-III colorectal cancer

Cited by 6 publications

References 76 publications

Immunotherapeutic IL-6R and targeting the MCT-1/IL-6/CXCL7/PD-L1 circuit prevent relapse and metastasis of triple-negative breast cancer

Immunotherapeutic IL-6R and targeting the MCT-1/IL-6/CXCL7/PD-L1 circuit prevent relapse and metastasis of triple-negative breast cancer

Interleukin-6-Positive Immune Cells as a Possible New Immunologic Marker Associated With the Colorectal Cancer Prognosis

Impact of severe postoperative complications on the prognosis of older patients with colorectal cancer: a two-center retrospective study

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