Characteristics of PBMC obtained from leukapheresis products and tumor biopsies of patients with non-small cell lung cancer

Yannelli, John R.; Tucker, Jo A.; Hidalgo, Giovanna E.; Perkins, Sara; Kryscio, Richard; Hirschowitz, Edward A.

doi:10.3892/or_00000588

Cited by 19 publications

(8 citation statements)

References 57 publications

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“…In humans, high numbers of CD4 + CD25 + Tregs were found in head and neck cancer [145], lung cancer [146, 147], pancreatic cancer [148], breast cancer [149], liver cancer [150], ovary cancer [151], and gastrointestinal cancer [152] either in the circulation or in the tumor itself. The appearance of Tregs at the tumor sites often correlates with poor prognosis of cancer patients [148, 151, 153, 154].…”

Section: Immunosuppressive Roles Of Foxp3+ Regulatory T Cells and mentioning

confidence: 99%

Tumor Evasion from T Cell Surveillance

Töpfer

Kempe

Müller

et al. 2011

BioMed Research International

144

131

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An intact immune system is essential to prevent the development and progression of neoplastic cells in a process termed immune surveillance. During this process the innate and the adaptive immune systems closely cooperate and especially T cells play an important role to detect and eliminate tumor cells. Due to the mechanism of central tolerance the frequency of T cells displaying appropriate arranged tumor-peptide-specific-T-cell receptors is very low and their activation by professional antigen-presenting cells, such as dendritic cells, is frequently hampered by insufficient costimulation resulting in peripheral tolerance. In addition, inhibitory immune circuits can impair an efficient antitumoral response of reactive T cells. It also has been demonstrated that large tumor burden can promote a state of immunosuppression that in turn can facilitate neoplastic progression. Moreover, tumor cells, which mostly are genetically instable, can gain rescue mechanisms which further impair immune surveillance by T cells. Herein, we summarize the data on how tumor cells evade T-cell immune surveillance with the focus on solid tumors and describe approaches to improve anticancer capacity of T cells.

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Section: Immunosuppressive Roles Of Foxp3+ Regulatory T Cells and mentioning

confidence: 99%

Tumor Evasion from T Cell Surveillance

Töpfer

Kempe

Müller

et al. 2011

BioMed Research International

144

131

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“…Peripheral blood mononuclear cells (PBMCs) are key cytokine-secreting immune cells, and their interactions with cancer cells may induce or suppress cancer-specific immune responses, including apoptosis induction and cytokine production, which contributing mostly to tumor progression [12], [21], [22]. Interactions between cancer cells and PBMCs occur in two main ways: through direct cell-to-cell contact, and through indirect cytokine-dependent mean.…”

Section: Introductionmentioning

confidence: 99%

Transforming Growth Factor-β1 and -β2 in Gastric Precancer and Cancer and Roles in Tumor-Cell Interactions with Peripheral Blood Mononuclear Cells In Vitro

Miao

Zeng

et al. 2013

PLoS ONE

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Transforming growth factor-β1 (TGF-β1) and -β2 are correlated with poorer prognosis in gastric cancer (GC), which act in both tumor and immune cells. However, their expressions in precancer and tumor-cell interactions with peripheral blood mononuclear cells (PBMCs) remain unclear. Protein levels of TGF-β1 and -β2 were analyzed by immunohistochemistry and corresponding mRNA levels were determined by quantitative real-time polymerase chain reaction in 93 surgical and biopsy specimens. Serum TGF-β concentration was detected by enzyme-linked immunosorbent assays. AGS and MKN45 cell lines were directly or indirectly cocultured with PBMCs in vitro. TGF-β and Smad molecules were detected after cocultures and the growths of GC cells and PBMCs were assessed by cell proliferation assay. The results showed positive staining for TGF-β1 was detected in 20% of control samples, 52.3% of precancer, 59.1% of early GC and 66.7% of advanced GC samples, correlated with lesion progression (χ2 = 9.487, P = 0.002). All tissues were positive for TGF-β2. TGF-β1 mRNA levels were increased in advanced cancers, while TGF-β2 increased earlier. TGF-β1 mRNA levels were higher in tumor than in peritumor, which positively correlated with Smad2 and Smad7. Serum TGF-β levels were significantly higher in patients with early and advanced cancers compared to controls (TGF-β1∶50.08±4.38 and 45.76±5.00 vs. 27.78±6.11 ng/mL; TGF-β2∶133.61±21.90 and 111.34±15.76 vs. 59.41±15.42 ng/mL, both P<0.05). The levels of TGF-β1 mRNA and cytokine secretion were higher in GC cells after direct coculture compared to indirect culture. TGF-β1 was decreased and TGF-β2 was increased in PBMCs after cocultures. Moreover, TGF-β1 inhibited the viability of PBMCs but not cancer cells. Collectively, neoplastic transformation may be an early event involving the increase of TGF-β1 in the general and local environment. TGF-β1 production is promoted by the direct interaction between GC cells and PBMCs, which might facilitate cancer development.

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“…Some studies reported significantly higher percentage of CD4 + CD25 + FoxP3 + Treg in patients with advanced/metastatic NSCLC compared to healthy donors29303132, whereas the high percentage of CD152 + CD4 + CD25 high FoxP3 + Tregs correlates with more advanced stage of disease2933. Furthermore, two recent studies demonstrated a prognostic value of peripheral CD4 + FoxP3 + Treg in stage I-III NSCLC patients3435.…”

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confidence: 99%

Prognostic value of circulating regulatory T cell subsets in untreated non-small cell lung cancer patients

Κotsakis

Koinis

Katsarou

et al. 2016

Sci Rep

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The role of the different circulating regulatory T-cells (Treg) subsets, as well as their correlation with clinical outcome of non-small cell lung cancer (NSCLC) patients is poorly understood. Peripheral blood from 156 stage III/IV chemotherapy-naive NSCLC patients and 31 healthy donors (HD) was analyzed with flow cytometry for the presence and functionality of CD4+ Treg subsets (naive, effector and terminal effector). Their frequencies were correlated with the clinical outcome. All CD4+ Treg subsets exhibited highly suppressive activity by TGF-β and IL-10 production. The percentages of naive Treg were found elevated in NSCLC patients compared to HD and were associated with poor clinical outcome, whereas the percentage of terminal effector Treg was lower compared to HD and higher levels were correlated with improved clinical response. At baseline, normal levels of naive and effector Treg were associated with longer overall survival (OS) compared to high levels, while the high frequency of the terminal effector Treg was correlated with longer Progression-Free Survival and OS. It is demonstrated, for first time, that particular CD4+ Treg subtypes are elevated in NSCLC patients and their levels are associated to the clinical outcome. The blocking of their migration to the tumor site may be an effective therapeutic strategy.

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Characteristics of PBMC obtained from leukapheresis products and tumor biopsies of patients with non-small cell lung cancer

Cited by 19 publications

References 57 publications

Tumor Evasion from T Cell Surveillance

Tumor Evasion from T Cell Surveillance

Transforming Growth Factor-β1 and -β2 in Gastric Precancer and Cancer and Roles in Tumor-Cell Interactions with Peripheral Blood Mononuclear Cells In Vitro

Prognostic value of circulating regulatory T cell subsets in untreated non-small cell lung cancer patients

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