Tumor-Associated Antigen Recognized by the 22-1-1 Monoclonal Antibody Encourages Colorectal Cancer Progression under the Scanty CD8+ T Cells

Oshikiri, Taro; Miyamoto, Masaki; Morita, Takayuki; Fujita, Mutsuhiro; Miyasaka, Yoshihiro; Senmaru, Naoto; Yamada, Hideshi; Takahashi, Toshiyuki; Horita, Shoichiro; Kondo, Satoshi

doi:10.1158/1078-0432.ccr-05-1257

Cited by 17 publications

(12 citation statements)

References 20 publications

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“…Interestingly, RCAS1 expression has been found more frequently in tumors with reduced or abnormal E-cadherin expression, thereby supporting evidence that both proteins may be critical for the mechanism of metastasis and recurrence in human colorectal cancer [13]. In addition, RCAS1 overexpression has been shown to induce the generation of the TN glycan antigen (N-acetyl-D-galactosamine, GalNAc) which, in the presence of scanty numbers of CD8 + T cells, may be a risk factor for the development of multiple liver metastases as well as being an independent prognostic factor for colorectal cancer [29]. Accordingly, RCAS1 expression was significantly correlated with the depth of invasion, lymph node metastasis, and histological stage in patients with esophageal carcinoma [15].…”

Section: Discussionmentioning

confidence: 59%

Clinical Significance of Tumor-associated Antigen RCAS1 Expression in Human Pancreatic Ductal Adenocarcinoma

et al. 2007

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Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that induces cell cycle arrest and/or apoptosis in RCAS1 receptor-expressing immune cells. The aim of the present study was to evaluate the clinical significance of RCAS1 expression in human pancreatic adenocarcinoma. Immunohistochemical analysis of RCAS1 expression was performed on paraffin-embedded tissue sections obtained from 76 pancreatic adenocarcinoma patients. RCAS1 positivity and overexpression and intensity of the staining were correlated with clinicopathological parameters, proliferative capacity and patient survival. Of the 76 adenocarcinoma patients, 65 (86%) tested positive for RCAS1; of these 65 RCAS1-positive cases, 36 (55%) showed RCAS1 overexpression. RCAS1 positivity was statistically significantly correlated with the histopathological grade of the tumor (P = 0.026), and it showed a trend to be correlated with tumor size (P = 0.071). RCAS1 intensity and overexpression of staining showed a trend to be correlated with the histopathological grade of the tumor (P = 0.061 and P = 0.089, respectively), whereas RCAS1 positivity and the overexpression and intensity of staining were not statistically significantly correlated with the proliferative capacity of the tumor or any other clinicopathological parameter examined nor with patients' survival. Our data provide evidence for the implication of RCAS1 in pancreatic neoplasia. However, the prediction of survival using RCAS1 expression as a marker seems uncertain for this type of cancer.

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Section: Discussionmentioning

confidence: 59%

Clinical Significance of Tumor-associated Antigen RCAS1 Expression in Human Pancreatic Ductal Adenocarcinoma

et al. 2007

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“…In colorectal cancer, there were 44 papers assessing CD8 [13,30,37,39,70,71,[81][82][83]85,86,92,93,98,108,109,112,114,116,117,121,122,125]. Of the nine studies that directly compared intratumoural CD8 assessment: three studies (625 patients) found IE significant where ST was not [75,81,121]; two studies (460 patients) found ST significant where IE was not [83,125]; three studies (1294 patients) found both IE and ST to be significant [71,85,98]; and one (291 patients) study compared IE assessment with combined assessment of IE and ST and found IE alone to be significant [37].…”

Section: Cd8 (Cytotoxic T-cells)mentioning

confidence: 99%

“…Fifteen independent studies (5475 patients) used an electronic method of assessment [13,59,82,83,85,86,[91][92][93]109,111,[117][118][119][120], of which 11 (4949 patients) found CD8 to be significant for survival [13,82,83,85,86,92,93,109,[117][118][119]. Twenty-two independent studies (5534 patients) used a manual method of assessment [9,30,37,39,70,71,81,84,88,89,98,108,110,[112][113][114][115][116][121][122][123]125], of which 16 (4689 patients) found CD8 to be significant for survival…”

Section: Cd8 (Cytotoxic T-cells)mentioning

confidence: 99%

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The local inflammatory response in colorectal cancer – Type, location or density? A systematic review and meta-analysis

Alexander

McMillan

Park

2020

Cancer Treatment Reviews

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The host anti-tumour inflammatory response is a strong prognostic indicator, and tumour infiltrating lymphocytes (TILs) are believed to have a complimentary role alongside TNM assessment in dictating future management. However, there is wide disagreement regarding the most efficacious and cost-effective method of assessment. Methods: A comprehensive literature search was performed of EMBASE, MedLine and PubMed as well as an assessment of references to identify all relevant studies relating to the assessment of the peri-tumoural inflammatory response or TILs and prognosis in colorectal cancer (CRC). A meta-analysis was performed of 67 studies meeting the REMARK criteria using RevMan software. Results: Intratumoural assessment of both CD3 and CD8 in CRC were significant for disease-free survival (DFS) (combined HRs 0.46; 95%CI: 0.39-0.54 and 0.54; 95%CI: 0.45-0.65), as well as overall survival (OS) and disease-specific survival (DSS). The same was true for assessment of CD3 and CD8 at the invasive margin (DFS: combined HRs 0.45; 95%CI: 0.33-0.61 and 0.51; 95%CI: 0.41-0.62). However, similar fixed effects summaries were also observed for H&E-based methods, like Klintrup-Makinen grade (DFS: HR 0.62; 95%CI: 0.43-0.88). Furthermore, inflammatory assessments were independent of MSI status. Conclusion: The evidence suggests that it is the density of a coordinated local inflammatory infiltrate that confers survival benefit, rather than any individual immune cell subtype. Furthermore, the location of individual cells within the tumour microenvironment does not appear to influence survival. The authors advocate a standardised assessment of the local inflammatory response, but caution against emphasizing the importance of any individual immune cell subtype.

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“…( 7,8 ) Immunohistochemical studies with tissue samples revealed that RCAS1 expression has been correlated significantly with poor overall survival in patients with several malignancies. ( 9–11 ) Ogushi et al . ( 12 ) provided the first in vivo evidence that EBAG9 was a tumor‐promoting and prognostic factor for renal cell carcinoma.…”

mentioning

confidence: 99%

EBAG9 inducing hyporesponsiveness of T cells promotes tumor growth and metastasis in 4T1 murine mammary carcinoma

Xiao

Liu

et al. 2009

Cancer Science

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The estrogen receptor-binding fragment-associated gene 9 (EBAG9) has been identified as an estrogen-responsive gene and was recently identified as a tumor-promoting and prognostic factor for renal cell carcinoma. We investigated whether EBAG9 expression was correlated with primary tumor growth and distant tumor metastasis in a murine breast carcinoma model. Knockdown expression of EBAG9 by small interfering RNA significantly suppressed tumor growth and metastasis in vivo in a highly malignant, spontaneously metastasizing 4T1 mouse mammary carcinoma model. 4T1 cells stably overexpressing EBAG9 developed larger and faster tumor growth and lung metastasis compared with parental 4T1 or 4T1 expressing vector alone. Strong specific cytotoxic T lymphocyte activity and enhanced γ-interferon and interleukin-2 productions were induced in mice that received EBAG9 small interfering RNA therapy. Gene silencing of EBAG9 prolonged the survival of tumor-bearing mice and induced more intensive infiltration of CD8 + T cells in tumor mass. EBAG9 induced apoptosis of T cells, enhanced glycogen synthase kinase 3β phosphorylation and inhibited γ-interferon production of T cells when T lymphocytes were cocultured with 4T1 cells overexpressing EBAG9. Furthermore, overexpression of EBAG9 in 4T1 cells was accompanied with enhanced expression of chemokine (C-X-C motif) receptor 4, which might be involved in tumor metastasis. Taken together, our results suggested that EBAG9 promoted primary 4T1 mammary carcinoma growth and distant metastasis, and EBAG9 small interfering RNA exerted overt regression of tumor growth and metastasis. These findings might provide insights into the mechanism through which tumors evade immunosurveillance and provide a strategy for therapeutic intervention of cancer metastases. (Cancer Sci 2009; 100: 961-969) E BAG9, an estrogen-responsive gene, was identified in MCF-7 human breast carcinoma cell line using a CpG-genomic binding site cloning method.(1) Its product was later found to be identical to RCAS1 (receptor-binding cancer antigen expressed on SiSo cells), a cancer cell-surface antigen implicated in immune escape.(2) EBAG9/RCAS1 expressed in estrogen target organs as well as several other tissues such as brain, liver, and kidney.(2) Published works also showed that EBAG9/RCAS1 was expressed in various malignancies such as breast, ovarian, prostate, and hepatocellular carcinomas.(3-6) RCAS1 reportedly acts as a ligand for a putative receptor present in various human cell lines and peripheral lymphocytes, such as T, B, and NK cells, and thus leads them to apoptosis, which might contribute to the escape of tumor cells from immune surveillance. (7,8) Immunohistochemical studies with tissue samples revealed that RCAS1 expression has been correlated significantly with poor overall survival in patients with several malignancies. (9)(10)(11) Ogushi et al. (12) provided the first in vivo evidence that EBAG9 was a tumor-promoting and prognostic factor for renal cell carcinoma. Their study showed that enhanced tumor gr...

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Tumor-Associated Antigen Recognized by the 22-1-1 Monoclonal Antibody Encourages Colorectal Cancer Progression under the Scanty CD8+ T Cells

Cited by 17 publications

References 20 publications

Clinical Significance of Tumor-associated Antigen RCAS1 Expression in Human Pancreatic Ductal Adenocarcinoma

Clinical Significance of Tumor-associated Antigen RCAS1 Expression in Human Pancreatic Ductal Adenocarcinoma

The local inflammatory response in colorectal cancer – Type, location or density? A systematic review and meta-analysis

EBAG9 inducing hyporesponsiveness of T cells promotes tumor growth and metastasis in 4T1 murine mammary carcinoma

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