Clinical Impact of Tumor-infiltrating Lymphocytes for Survival in Curatively Resected Stage IV Colon Cancer with Isolated Liver or Lung Metastasis

Lee, Won Suk; Kang, Myunghee; Baek, Jeong‐Heum; Lee, Jae Ik; Ha, Seung Yeon

doi:10.1245/s10434-012-2752-1

Cited by 51 publications

(64 citation statements)

References 37 publications

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“…Although the density of TILs in the primary tumor was found to be associated with the chemotherapeutic outcome in this study, the correlation between the density of TILs in the metastatic tumor, which is a target for chemotherapy, and the chemotherapeutic outcome is unclear. A previous report described a strong correlation between the density of TILs in the primary tumor and that in metastatic tumors (28). Therefore, the evaluation of TILs in the primary tumor may serve as a substitution for the evaluation of TILs in metastatic tumors.…”

Section: Discussionmentioning

confidence: 95%

Tumor-infiltrating Lymphocytes Predict the Chemotherapeutic Outcomes in Patients with Stage IV Colorectal Cancer

Shibutani

Maeda

Nagahara

et al. 2018

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Abstract. Background Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide (1). About 20-25% of patients with newly diagnosed CRC present with distant metastases (2-4), and only a small population of these patients can undergo curative operation (5). For patients with unresectable metastatic tumors, the standard treatment is systemic chemotherapy. As mentioned in the ESMO clinical practice guidelines (4), an individualized approach to clinical decision-making should be adopted according to the patient's stratification. Therefore, numerous attempts have been made to identify useful prognostic markers for accurate patient stratification.Anticancer immunity is known to affect cancer progression (6). Tumor-infiltrating lymphocytes (TILs), which reflect the immune status of the host (7), have been reported to correlate with the clinical outcome, including the chemotherapeutic outcome in patients with various types of cancer (8-10). However, the method of measuring TILs has differed among previous reports (11)(12)(13)(14)(15). Recently, a new method of measuring TILs in breast cancer was proposed by the International TILs Working Group, using H-E-stained sections (16). In the current study, we applied this method to CRC.The aim of the present study was to evaluate the significance of the TILs in the primary tumor as a marker for predicting the chemotherapeutic outcome in patients with stage IV CRC using the method proposed by the International TILs Working Group. Patients and MethodsPatients. We retrospectively reviewed a database of 57 patients who underwent palliative combination chemotherapy for unresectable metastatic colorectal cancer after resection of the primary tumor at

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Section: Discussionmentioning

confidence: 95%

Tumor-infiltrating Lymphocytes Predict the Chemotherapeutic Outcomes in Patients with Stage IV Colorectal Cancer

Shibutani

Maeda

Nagahara

et al. 2018

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“…TILs have been identified in various types of tumors, including lung cancer. Their existence has been found to be associated with decreased tumor progression (25), induction of responses to chemotherapy (26,27) and increased lifetime of patients (28). TILs derived from neonatal cord blood mononuclear cells induced marked human lung and cervical tumor remission in NOD/SCID mice, and the antitumor effect was accompanied with a high infiltration of CD3 + T cells in tumors and a marked induction of apoptotic cell death (25).…”

Section: Discussionmentioning

confidence: 99%

Immune reconstitution from peripheral blood mononuclear cells inhibits lung carcinoma growth in NOD/SCID mice

Liu

et al. 2014

Oncology Letters

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Drug resistance and immune deficiency are important factors for the poor prognosis of lung carcinoma. The present study explored the possible protective effect of immune reconstitution from peripheral blood mononuclear cells (PBMCs) on multi-drug-resistant human lung carcinoma Am1010 cells in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. The inoculated tumor fragments grew rapidly in the NOD/SCID mice. The growth was significantly inhibited by intraperitoneal injection of PBMCs. In the mice injected with PBMCs, numerous CD3+ and CD8+ cells, but less CD4+ cells, were found in spleen and tumor tissues. These data suggest that PBMC transplantation inhibits lung carcinoma progression via the reconstitution of the immune system, particularly of cytotoxic T lymphocytes.

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“…Initial studies showed that NK cells from patients with ovarian cancer have poor cytotoxic functions against tumors [31,32,33,34], and one study reported that high numbers of infiltrating NK cells in tumors was associated with a worse prognosis [35], which is in conflict with other reports on NK cell infiltration and outcome that focus on different types of cancers [36]. Studies have shown that the antitumor function of NK cells from peripheral blood of patients with ovarian cancer can be significantly augmented by in vitro stimulation with recombinant IL-2 [31,32], and that primary malignant ovarian cells are susceptible to killing by allogeneic NK lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

Natural Killer Cells Response to IL-2 Stimulation Is Distinct between Ascites with the Presence or Absence of Malignant Cells in Ovarian Cancer Patients

Silva

Yoshida

Cardozo

et al. 2017

IJMS

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Peritoneal ascites are a distinguishable feature of patients with advanced epithelial ovarian cancer (EOC). The presence of different lymphocyte subsets has been reported in EOC-associated ascites, which also can or not contain malignant cells. The goal of this study was to analyze the functional characteristics of natural killer (NK) cells from EOC-associated ascites in terms of their expression of activating receptors and ascites’ contents of lymphocyte subtypes, cytokine profile and presence of EOC cells. NK cell function was evaluated by the expression of the degranulation marker CD107a in resting and interleukin (IL)-2 stimulated NK cells from ascites and blood. Degranulation of NK cells from EOC cell-free ascites was significantly (p < 0.05) higher than all the other groups, either in their resting state or after IL-2 stimulation, suggesting a previous local stimulation. In contrast, treatment with IL-2 had no effect on NK cells from ascites with EOC cells. The amount of regulatory T cells was significantly higher in ascites with EOC cells compared to EOC cell-free ascites. Ascites with EOC cells also had higher levels of tumor necrosis factor (TNF)-α, suggesting inflammation related to the malignancy. In conclusion, the functional performance of NK cells was distinct between EOC cell-free ascites and ascites with EOC cells. The impairment of NK cell response to IL-2 in ascites with EOC cells was consistent with an immunosuppressive tumor microenvironment.

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Clinical Impact of Tumor-infiltrating Lymphocytes for Survival in Curatively Resected Stage IV Colon Cancer with Isolated Liver or Lung Metastasis

Abstract: High density of CD45RO(+) TILs showed independent prognostic significance for OS. This result may help to improve the prognostication of curatively resected stage IV colon cancer.

Cited by 51 publications

References 37 publications

Tumor-infiltrating Lymphocytes Predict the Chemotherapeutic Outcomes in Patients with Stage IV Colorectal Cancer

Tumor-infiltrating Lymphocytes Predict the Chemotherapeutic Outcomes in Patients with Stage IV Colorectal Cancer

Immune reconstitution from peripheral blood mononuclear cells inhibits lung carcinoma growth in NOD/SCID mice

Natural Killer Cells Response to IL-2 Stimulation Is Distinct between Ascites with the Presence or Absence of Malignant Cells in Ovarian Cancer Patients

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