Reciprocal CD4+ T-Cell Balance of Effector CD62Llow CD4+ and CD62LhighCD25+ CD4+ Regulatory T Cells in Small Cell Lung Cancer Reflects Disease Stage

Koyama, K.; Kagamu, Hiroshi; Miura, Satoru; Hiura, Takeshi; Miyabayashi, Takao; Itoh, R.; Kuriyama, Hideyuki; Tanaka, Hiroshi; Tanaka, Junta; Yoshizawa, Hirohisa; Nakata, Koh; Gejyo, Fumitake

doi:10.1158/1078-0432.ccr-08-1156

Cited by 113 publications

(81 citation statements)

References 46 publications

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“…6 Furthermore, the balance between T E s and Tregs in tumor tissues and among peripheral blood mononuclear cells was correlated with the prognosis of cancer patients. 7,8 These findings suggested that Tregs suppress antitumor immunity and contribute to tumor progression. Indeed, recent studies demonstrated that the inhibition of Tregs enhances antitumor immunity and slows tumor progression.…”

Section: Introductionmentioning

confidence: 95%

“…5 Previously, we reported that the effector-tosuppressor T-cell ratio was strongly correlated with overall survival in small-cell lung cancer patients. 8 Accumulating evidence suggests that Tregs may suppress antitumor immunity and contribute to tumor progression. Although lymphodepleting regimens may affect the number and functions of Tregs, the effect of lymphodepletion on Tregs is poorly understood.…”

Section: Whole-body Irradiation Increases the Percentage Of Cd4mentioning

confidence: 99%

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Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia

Baba

Watanabe

Saida

et al. 2012

Blood

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Section: Introductionmentioning

confidence: 95%

Section: Whole-body Irradiation Increases the Percentage Of Cd4mentioning

confidence: 99%

Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia

Baba

Watanabe

Saida

et al. 2012

Blood

Self Cite

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“…Still, a number of human tumors contain immune cells and a higher number of T cells and macrophages correlates with favorable outcomes in patients (56). Long-term survivors of SCLC also maintained a high ratio of effector T cells to regulatory T cells (57). Our group has shown that inhibition of the "marker of self" CD47 [recently reviewed in (58)] can activate the innate immune system and induce the phagocytosis of SCLC in allograft and PDX models (23).…”

Section: Non-cancer Cells In Sclc Tumorsmentioning

confidence: 97%

Tumor heterogeneity in small cell lung cancer defined and investigated in pre-clinical mouse models

Shue¹,

Lim²,

Sage³

2018

Transl. Lung Cancer Res.

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Small cell lung carcinoma (SCLC) is a neuroendocrine subtype of lung cancer characterized by its fast growth and aggressive nature. SCLC development is strongly associated with heavy cigarette smoking. In a majority of cases, SCLC tumors have already metastasized to distant sites at the time of first diagnosis. Except in rare cases when tumors are diagnosed early, treatment options are limited and usually consist of several rounds of chemotherapy with cisplatin/ carboplatin and etoposide. While this chemotherapy regimen often results in significant response and tumor shrinkage, relapse is usually quite rapid. A number of excellent reviews have recently discussed the key clinical features of SCLC and the current lack of efficient treatment despite a large number of clinical trials in the past three decades (1-4). New therapeutic approaches, including immunotherapies, are promising but at the time this review is written, there are still no approved targeted therapies for SCLC [reviewed in (5-8)].Here we discuss emerging data in the field on the role of tumor heterogeneity in the growth of SCLC and the response of these tumors to therapy, and how mouse models have been used to identify such tumor heterogeneity and investigate its role. We use the term "intertumoral" heterogeneity to describe how SCLC tumors in patients or mice evolve differently at the genetic and epigenetic level during tumor progression and metastasis. We use the term "intratumoral" heterogeneity to describe the different subpopulations of cells within tumors at any given time; in Abstract: Small cell lung carcinoma (SCLC) is a fast-growing, highly metastatic form of lung cancer. A major difference between SCLC and other forms of lung cancer is that SCLC tumors often respond well to chemotherapy initially; unfortunately, resistant tumors rapidly recur. In addition, despite a large number of clinical trials with a variety of therapeutic agents, little progress has been achieved in the past three decades in improving the survival of SCLC patients. These clinical observations indicate that SCLC tumors have a high degree of plasticity and rapid adaptability to changes in growth conditions. Here we consider recent evidence pointing to several levels of heterogeneity in SCLC that may explain the ability of these tumors to adjust to different microenvironment and therapeutics. In particular, we review new data pointing to the existence of several subpopulations of tumor cells that interact with each other to promote tumor growth.We also discuss how SCLC tumors that look similar at the histopathological level may actually represent distinct subtypes of tumors and how these differences impact the response to specific therapeutic agents.A better understanding of genetic and cellular heterogeneity will guide the development of personalized approaches to help SCLC patients.

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“…It was shown that significantly more immune effector T cells (Teff) were detected in limited-stage SCLC compared with extendedstaged disease [Koyama et al 2008]. Long-term survivors of SCLC maintained a high Teff to Treg cell ratio, whereas patients with recurrent disease exhibited a low Teff:Treg ratio.…”

Section: Small Cell Lung Cancermentioning

confidence: 99%

Checkpoint inhibitors in lung cancer: latest developments and clinical potential

2016

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Lung cancer is the leading cause of cancer death in the United States. The vast majority of patients are diagnosed with metastatic disease with a 5-year survival rate of less than 5%. After first-line chemotherapy or biomarker-matched targeted therapy, only suitable for a small group of patients, further systemic therapy options rendered very limited, if any, benefit until recently. Checkpoint inhibitors have significantly improved outcomes in patients with metastatic non-small cell lung cancer (NSCLC) and are currently an established secondline therapeutic option. In this manuscript, we review the mechanism of action of checkpoint inhibitors, present the available data with approved and experimental agents, discuss the progress that has already been made in the field, as well as toxicity awareness, and future perspectives.

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Reciprocal CD4+ T-Cell Balance of Effector CD62Llow CD4+ and CD62LhighCD25+ CD4+ Regulatory T Cells in Small Cell Lung Cancer Reflects Disease Stage

Cited by 113 publications

References 46 publications

Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia

Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia

Tumor heterogeneity in small cell lung cancer defined and investigated in pre-clinical mouse models

Checkpoint inhibitors in lung cancer: latest developments and clinical potential

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