Prognostic significance of CD8+ T cell and macrophage peritumoral infiltration in colorectal cancer

Funada, Y.; Noguchi, Tsuyoshi; Kikuchi, Ryuichi; Takeno, Shinsuke; Uchida, Yuzo; Gabbert, Helmut E.

doi:10.3892/or.10.2.309

Cited by 122 publications

(138 citation statements)

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“…[12][13][14] Some studies relying on immunohistochemical staining of human colorectal cancers, in fact, indicate that macrophages along the tumor margin [31][32][33] and macrophages expressing VEGF 34 are associated with a good prognosis. Others have suggested that macrophages in colorectal cancer may have co-stimulatory functions in antitumor immunity 35 or may be able to induce tumor cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages

et al. 2016

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Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been implicated in promoting colon cancer; however, the mechanisms behind this effect are poorly understood. We have previously demonstrated that deficiency of CCR6 is associated with decreased tumor macrophage accumulation in a model of sporadic intestinal tumorigenesis. In this study, we aimed to determine the role of stromal CCR6 expression in a murine syngeneic transplantable colon cancer model. We show that deficiency of host CCR6 is associated with decreased growth of syngeneic CCR6-expressing colon cancers. Colon cancers adoptively transplanted into CCR6-deficient mice have decreased tumor-associated macrophages without alterations in the number of monocytes in blood or bone marrow. CCL20, the unique ligand for CCR6, promotes migration of monocytes in vitro and promotes accumulation of macrophages in vivo. Depletion of tumor-associated macrophages decreases the growth of tumors in the transplantable tumor model. Macrophages infiltrating the colon cancers in this model secrete the inflammatory mediators CCL2, IL-1a, IL-6 and TNFa. Ccl2, Il1a and Il6 are consequently downregulated in tumors from CCR6-deficient mice. CCL2, IL-1a and IL-6 also promote proliferation of colon cancer cells, linking the decreased macrophage migration into tumors mediated by CCL20-CCR6 interactions to the delay in tumor growth in CCR6-deficient hosts. The relevance of these findings in human colon cancer is demonstrated through correlation of CCR6 expression with that of the macrophage marker CD163 as well as that of CCL2, IL1a and TNFa. Our findings support the exploration of targeting the CCL20-CCR6 pathway for the treatment of colon cancer.

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Section: Discussionmentioning

confidence: 99%

Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages

et al. 2016

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“…Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of variety of cancers, including breast and cervical cancers and transitional cell carcinomas [19] [20][21][22][23]. In contrast, intratumoral TAMs count has been correlated with depth of invasion, lymph node metastasis, and staging of CRC, suggesting that intratumoral macrophages cause cancer cells to have a more aggressive behavior [24,25].…”

Section: Tumor Associated Macrophagesmentioning

confidence: 99%

Immune Cells in Colorectal Cancer: Prognostic Relevance and Role of MSI

Deschoolmeester

Baay

Lardon

et al. 2011

Cancer Microenvironment

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There is growing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of solid tumors. Colorectal cancer (CRC) results from the cumulative effect of sequential genetic alterations, leading to the expression of tumor-associated antigens possibly inducing a cellular antitumor immune response. It is well recognized that cytotoxic lymphocytes (CTLs) constitute one of the most important effector mechanisms of anti-tumor-immunity. However, their potential prognostic influence in CRC remains controversial. In addition, other key players like natural killer cells, tumor associated macrophages and regulatory T cells play an important role in the immune attack against CRC and need further investigation. This review will mainly focus on the role of the adaptive immune system in CRC and particularly in regard to microsatellite instability.

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“…On the other hand, the prognoses of patients being at the same stage of this system can differ considerably, thus more accurate and sensitive prognostic factors are needed. Many clinical and pathological features, patient-and tumor-related variables are still investigated (5)(6)(7)(8). Recent studies of predictive significance of genetic alterations and molecular factors have provided very promising results (8)(9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Clinical factors in prediction of prognosis after anterior resection with total mesorectal excision for carcinoma of the rectum

Szynglarewicz¹,

Matkowski²,

Forgacz³

et al. 2007

Oncol Rep

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Abstract. The aim of the study was to estimate the long-term results and the prognostic value of clinical and pathological factors following R0 anterior resection with total mesorectal excision (TME). Ninety-eight consecutive patients with histologically confirmed rectal cancer were studied prospectively with five-year follow-up. Survival was calculated using the Kaplan-Meier method and differences between curves were tested by the log-rank test. Multivariate analysis was performed using the Cox regression model. Recurrence-free survival (RFS) was 63.6%. Mean time of recurrence was 13.8 months (range 3-38). Local recurrence rate was 7.8% with the mean time of 12.7 months (range 3-25). In univariate analysis Dukes' stage (RFS for stage: A=93.2%; B=53.8%; C=26.3%) and preoperative CEA serum level (s-CEA) (for s-CEA ≤5 ng/ml RFS=93.8%; for s-CEA >5 ng/ml RFS = 5.9%) significantly influenced survival (P<0.005 and P<0.00001). These parameters were also found to be independent prognostic factors in multivariate analysis (P<0.05 and P<0.00001). Survival was worse in older female patients with low-localised poorly differentiated tumors; however, those variables had not significant impact on prognosis. Neither symptom duration nor mucinous histology was significantly related to survival. Using TME technique a low local recurrence rate resulting in improved survival can be achieved. Apart from clinicopathological staging, elevated s-CEA can identify patients with poor prognosis. In addition to TME adjuvant therapy for this high-risk group should be considered.

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Prognostic significance of CD8+ T cell and macrophage peritumoral infiltration in colorectal cancer

Cited by 122 publications

References 0 publications

Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages

Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages

Immune Cells in Colorectal Cancer: Prognostic Relevance and Role of MSI

Clinical factors in prediction of prognosis after anterior resection with total mesorectal excision for carcinoma of the rectum

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