Intratumoural FOXP3-positive regulatory T cells are associated with adverse prognosis in radically resected gastric cancer

Perrone, Giuseppe; Ruffini, Pier Adelchi; Catalano, Vincenzo; Spino, Cathie; Santini, Daniele; Muretto, Pietro; Spoto, Chiara; Zingaretti, Costantino; Sisti, Valerio; Alessandroni, Paolo; Giordani, Paolo; Cicetti, Andrea; Demidio, S.; Morini, Sergio; Ruzzo, Annamaria; Magnani, Mauro; Tonini, Giuseppe; Rabitti, Carla; Graziano, Francesco

doi:10.1016/j.ejca.2008.05.017

Cited by 184 publications

(141 citation statements)

References 39 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…A negative prognostic impact of tumor-infiltrating regulatory T cells has been shown for several types of cancer, including gastric cancer. [46][47][48][49][50][51][52][53] The comprehensive mutational analysis in this study is in concordance with the findings of other studies. 54 That we could not find a correlation between the genomic profile and expression of immune checkpoint receptors is probably due to the low frequencies of the analyzed mutations.…”

Section: Cd25supporting

confidence: 82%

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

et al. 2015

View full text Add to dashboard Cite

Remarkable efficacy of immune checkpoint inhibition has been reported for several types of solid tumors and early studies in gastric adenocarcinoma are promising. A detailed knowledge about the natural biology of immune checkpoints in gastric adenocarcinoma is essential for clinical and translational evaluation of these drugs. This study is a comprehensive analysis of cytotoxic T lymphocyte associated molecule 4 (CTLA-4) and programmed death 1 ligand 1 (PD-L1) expression in gastric adenocarcinoma. PD-L1 and CTLA-4 were stained on tumor sections of 127 Caucasian patients with gastric adenocarcinoma by immunohistochemistry (IHC) and somatic mutation profiling was performed using targeted nextgeneration sequencing. Expression of PD-L1 and CTLA-4 on lymphocytes in tumor sections, tumordraining lymph nodes (TDLN) and peripheral blood were studied by flow-cytometry and immune-fluorescence microscopy in an additional cohort. PD-L1 and CTLA-4 were expressed in 44.9% (57/ 127) and 86.6% (110/127) of the analyzed gastric adenocarcinoma samples, respectively. Positive tumor cell staining for PD-L1 or CTLA-4 was associated with inferior overall survival. Somatic mutational analysis did not reveal a correlation to expression of PD-L1 or CTLA-4 on tumor cells. Expression of PD-1 (52.2%), PD-L1 (42.2%) and CTLA-4 (1.6%) on tumor infiltrating T cells was significantly elevated compared to peripheral blood. Of note, PD-1 and PD-L1 were expressed far higher by tumor-infiltrating lymphocytes than CTLA-4. In conclusion, specific immune checkpoint-inhibitors should be evaluated in this disease and the combination with molecular targeted therapies might be of benefit. An extensive immune monitoring should accompany these studies to better understand their mode of action in the tumor microenvironment.Abbreviations: CTLA-4, cytotoxic T lymphocyte associated molecule 4; PBMC, peripheral blood mononuclear cells; PD-1, programmed death 1; PD-L1, programmed death 1 ligand 1; TDLN, tumor-draining lymph nodes; UICC, Union International Contre le Cancer.

show abstract

Section: Cd25supporting

confidence: 82%

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Evidence suggests that Tregs contribute to immune suppression by dampening the antitumor immunity elicited by CD4 + T cells, CD8 + T cells, dendritic and NK cells (24)(25)(26)(27). Treg accumulations in tumors and peripheral blood have been linked to unfavorable disease outcomes of tumor invasion, recurrence and shortened survival for many human solid tumors, including hepatocellular carcinoma, ovarian carcinoma, pancreatic ductal carcinoma, cervical cancer, NSCLC and breast cancer (28)(29)(30)(31)(32)(33). In these tumors, Tregs suppress antitumor immunity and mediate immune tolerance that favors tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Wang

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Previous studies have reported that regulatory T cells (Tregs), which are physiologically engaged in the maintenance of immunological self-tolerance, have a critical role in the regulation of the antitumor immune response. Targeting Tregs has the potential to augment cancer vaccine approaches. The current study therefore aimed to evaluate the role of cytokine-induced killer (CIK) cell infusion in modulating Tregs in patients with non-small cell lung cancer (NSCLC). A total of 15 patients with advanced NSCLC were treated by an infusion of CIK cells derived from autologous peripheral blood mononuclear cells (PBMCs). By using flow cytometry and liquid chip analysis, subsets of T cells and natural killer (NK) cells in peripheral blood, and plasma cytokine profiles in the treated patients, were analyzed at 2 and 4 weeks after CIK cell infusion. Cytotoxicity of PBMCs (n=15) and NK cells (n=6) isolated from NSCLC patients was evaluated before and after CIK cell therapy. Progression-free survival (PFS) and overall survival (OS) were also assessed. Analysis of the immune cell populations before and after treatment showed a significant increase in NK cells (P<0.05) concomitant with a significant decrease in Tregs (P<0.01) at 2 weeks post-infusion of CIK cells compared with the baseline. NK group 2D receptor (NKG2D) expression on NK cells was also significantly increased at 2 weeks post-infusion compared with the baseline (P<0.05). There was a positive correlation between NKG2D expression and the infusion number of CIK cells (P<0.05).

show abstract

“…Also, the ratio of Tregs in some types of cancers such as gastric cancer is abnormally high (Perrone et al 2008). So, several experiments were aimed at increasing cytotoxic T cells and decreasing Tregs in tumor tissue.…”

Section: Effects On T Regulatory (Tregs) Cellsmentioning

confidence: 99%

The melatonin immunomodulatory actions in radiotherapy

et al. 2017

View full text Add to dashboard Cite

Radiotherapy has a key role in cancer treatment in more than half of patients with cancer. The management of severe side effects of this treatment modality is a limiting factor to appropriate treatment. Immune system responses play a pivotal role in many of the early and late side effects of radiation. Moreover, immune cells have a significant role in tumor response to radiotherapy, such as angiogenesis and tumor growth. Melatonin as a potent antioxidant has shown appropriate immune regulatory properties that may ameliorate toxicity induced by radiation in various organs. These effects are mediated through various modulatory effects of melatonin in different levels of tissue reaction to ionizing radiation. The effects on the DNA repair system, antioxidant enzymes, immune cells, cytokines secretion, transcription factors, and protein kinases are most important. Moreover, anti-cancer properties of melatonin may increase the therapeutic ratio of radiotherapy. Clinical applications of this agent for the management of malignancies such as breast cancer have shown promising results. It seems anti-proliferative, anti-angiogenesis, and stimulation or suppression of some immune cell responses are the main anti-tumor effects of melatonin that may help to improve response of the tumor to radiotherapy. In this review, the effects of melatonin on the modulation of immune responses in both normal and tumor tissues will be discussed.

show abstract

Intratumoural FOXP3-positive regulatory T cells are associated with adverse prognosis in radically resected gastric cancer

Cited by 184 publications

References 39 publications

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

The melatonin immunomodulatory actions in radiotherapy

Contact Info

Product

Resources

About