CD8+ Tumor-Infiltrating Lymphocytes Together with CD4+ Tumor-Infiltrating Lymphocytes and Dendritic Cells Improve the Prognosis of Patients with Pancreatic Adenocarcinoma

Fukunaga, Akira; Miyamoto, Masaki; Cho, Yasushi; Murakami, Soichi; Kawarada, Yo; Oshikiri, Taro; Kato, Kentaro; Kurokáwa, Tomonori; Suzuoki, Masato; Nakakubo, Yoshihiro; Hiraoka, Kenzo; Itoh, Tomoo; Morikawa, Toshiaki; Okushiba, Shunichi; Kondo, Satoshi; Katoh, Hiroyuki

doi:10.1097/00006676-200401000-00023

Cited by 483 publications

(420 citation statements)

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“…In the presence of a relatively high level of CD4 þ T-cell infiltration, patients with a sufficient number of tumour-infiltrating CD8 þ T cells demonstrated a significantly better prognosis. We have previously demonstrated a similar synergistic effect between tumour-infiltrating CD8 þ T cells and CD4 þ T cells in oesophageal squamous cell carcinoma and pancreatic adenocarcinoma Fukunaga et al, 2004). The present study is the first report demonstrating such an effect directly observed in resected human specimens.…”

Section: Discussionsupporting

confidence: 81%

“…oesophageal squamous cell carcinoma Nakakubo et al, 2003;Oshikiri et al, 2003;Fukunaga et al, 2004). However, in NSCLC, the role of TILs for the survival of patients is still controversial.…”

Section: Discussionmentioning

confidence: 99%

“…Among TILs, most CD8 þ T cells are cytotoxic T lymphocytes that recognise particular tumour-associated antigens presented on MHC class I molecules at the cancer cell surface and possess the ability to destroy cancer cells directly. The favourable prognostic significance of the presence of tumour-infiltrating CD8 þ T cells was previously reported in a variety of cancers, including colorectal cancer, oesophageal cancer, pancreatic cancer, bile duct cancer and gallbladder cancer (Naito et al, 1998;Nakano et al, 2001;Schumacher et al, 2001;Cho et al, 2003;Nakakubo et al, 2003;Oshikiri et al, 2003;Fukunaga et al, 2004). In NSCLC, however, the relationship between patient prognosis and the presence of TILs is still obscure.…”

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confidence: 92%

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Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma

et al. 2006

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The purpose of this study was to clarify the relationship between the number of tumour-infiltrating T lymphocytes and the clinicopathological features and clinical outcome in patients with non-small-cell lung cancer (NSCLC). Tissue specimens from 109 patients who underwent surgical resection for NSCLC were immunohistochemically analysed for CD4 and CD8 expression. Patients were classified into two groups according to whether their tumours exhibited a 'high' or 'low' level of CD8 þ or CD4 þ lymphocyte infiltration. Although the level of infiltration by CD8 þ T cells alone had no prognostic significance, the survival rate for patients with both 'high' CD8 þ and 'high' CD4 þ T-cell infiltration was significantly higher than that for the other groups (log-rank test, P ¼ 0.006). Multivariate analysis indicated that concomitant high CD8 þ and high CD4 þ T-cell infiltration was an independent favourable prognostic factor (P ¼ 0.0092). In conclusion, the presence of high levels of both CD8 þ T cells and CD4 þ T cells is a significant indicator of a better prognosis for patients with NSCLC, and cooperation between these cell populations may allow a significantly more potent antitumour response than either population alone.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 92%

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Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma

et al. 2006

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“…[16][17][18] Like Zhang et al, 10 we demonstrate (in two separate laboratories using independent testing and analysis) that intraepithelial CD3 þ tumor-infiltrating lymphocytes correlate with disease-specific survival in serous ovarian carcinomas. Likewise, we have confirmed the results of two recent studies 9,11 by demonstrating that intraepithelial CD8 þ tumorinfiltrating lymphocytes correlate with disease-specific survival in the entire study cohort (including all stages and histologies), as well as in the subset of serous ovarian carcinomas.…”

Section: Discussionsupporting

confidence: 55%

“…The prognostic significance of the host immune response, as defined by the presence of tumor-infiltrating lymphocytes, has been studied in ovarian cancer [8][9][10][11] and other cancers [12][13][14][15][16][17][18] Zhang et al 10 identified intratumoral (later named intraepithelial) CD3 þ T-cell infiltration to be an independent prognostic factor in 186 advanced ovarian cancers. Curiel et al 8 demonstrated that infiltration of CD4 þ CD25 þ regulatory T-cells carried a worse prognosis in ovarian cancer.…”

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confidence: 99%

Intraepithelial T cells and prognosis in ovarian carcinoma: novel associations with stage, tumor type, and BRCA1 loss

et al. 2009

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Intraepithelial tumor-infiltrating T cells have been correlated with improved outcomes in ovarian carcinoma, however, it is not known whether there is an association with disease stage, histological subtype, or BRCA mutation/expression. Two case series of ovarian carcinomas were included in the study; a retrospective series of 500 patients, and 40 prospectively collected cases fully characterized for BRCA1 mutation status and expression. Intraepithelial immune cells were assessed as present or absent by immunohistochemical staining of tissue microarrays. In the retrospective case series, the presence of intraepithelial CD8 þ T-cells correlated with improved disease-specific survival (P ¼ 0.027), whereas intraepithelial CD3 þ T cells did not (P ¼ 0.49). For serous ovarian carcinomas, the presence of intraepithelial CD3 þ and CD8 þ T-cells correlated with improved disease-specific survival (P ¼ 0.0016 and Pr0.0001, respectively). The presence of intraepithelial CD8 þ T cells was not associated with improved survival in endometrioid or clear cell carcinomas. On multivariate analysis, disease stage and CD8 þ T cells were found to be independently predictive of improved disease-specific survival, whereas grade, age at surgery, and type of adjuvant treatment were not. In the prospective patient cohort, intraepithelial CD8 þ T-cells correlated with the presence of mutation or loss of expression of BRCA1 through promoter methylation (P ¼ 0.019). Intraepithelial CD8 þ tumor-infiltrating T-cells correlate with improved clinical outcomes for all stages of ovarian cancer; this association is restricted to the serous ovarian cancer subtype, and is an independent prognostic factor on multivariate analysis. The presence of intraepithelial CD8 þ T cells also significantly correlates with loss of BRCA1. rates to chemotherapy and the demonstrated improvements in median overall survival, fewer than 40% of patients with advanced disease survive to 5 years. 3 Many potential molecular prognostic factors in ovarian cancer have been investigated (eg HER2, TP53). 4 Most factors were identified in small studies and have not been reproduced or independently validated, precluding clinical utility. In addition, mutations of the BRCA1 and 2 tumor suppressor genes have been associated with improved clinical outcomes 5-7 but the biologic mechanisms underlying these findings are not well understood to date.The prognostic significance of the host immune response, as defined by the presence of tumor-infiltrating lymphocytes, has been studied in ovarian

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Platelet‐to‐lymphocyte ratio could be a promising prognostic biomarker for survival of colorectal cancer: a systematic review and meta‐analysis

Peng

Kang

et al. 2016

FEBS Open Bio

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Inflammation is one of the most important causes leading to colorectal carcinogenesis, and inflammatory biomarkers such as the platelet‐to‐lymphocyte ratio ( PLR ) might predict survival in colorectal cancer ( CRC ). However, the prognostic value of PLR in CRC patients remains controversial. The prognostic value of PLR was comprehensively analyzed in 12 articles including 3541 CRC patients (10 for overall survival ( OS ), seven for disease‐free survival ( DFS ), three for recurrence‐free survival ( RFS ), and three for cancer‐specific survival ( CSS )) in this study. The overall pooled hazard ratios ( HR s) of PLR for OS , DFS , and CSS were significant at 1.29 (95% confidence interval, CI = 1.13–1.47, P H = 0.149), 1.43 (95% CI = 1.03–1.97, P H = 0.025), and 1.26 (95% CI = 1.04–1.52, P H = 0.223), respectively. However, there was no evidence of significance for RFS ( HR = 1.29, 95% CI = 0.98–1.70, P H = 0.231) in our study. Stratified analyses indicated elevated PLR was a predictor of poor OS (metastatic patients) and DFS (Caucasian population) and was also significantly associated with OS in univariate analysis ( HR = 1.35, 95% CI = 1.14–1.60, P H = 0.532) and those only treated surgically ( HR = 1.37, 95% CI = 1.10–1.70, P H = 1.080). However, our findings indicated that elevated PLR is a promising prognostic biomarker for colorectal cancer, especially in metastatic Caucasian CRC patients.

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CD8+ Tumor-Infiltrating Lymphocytes Together with CD4+ Tumor-Infiltrating Lymphocytes and Dendritic Cells Improve the Prognosis of Patients with Pancreatic Adenocarcinoma

Abstract: In pancreatic adenocarcinoma, the presence of CD4+ TILs together with CD8+ TILs serves as a good indicator of the patient's outcome after surgical treatment.

Cited by 483 publications

References 17 publications

Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma

Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma

Intraepithelial T cells and prognosis in ovarian carcinoma: novel associations with stage, tumor type, and BRCA1 loss

Platelet‐to‐lymphocyte ratio could be a promising prognostic biomarker for survival of colorectal cancer: a systematic review and meta‐analysis

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