Janus or Hydra: The Many Faces of T Helper Cells in the Human Tumour Microenvironment

Guisier, Florian; Barros-Filho, Mateus Camargo; Rock, Leigha D.; Strachan-Whaley, Megan; Marshall, Erin A.; Dellaire, Graham; Lam, Wan L.

doi:10.1007/978-3-030-35723-8_3

Cited by 10 publications

(14 citation statements)

References 168 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Their characteristics at enrollment were as expected for a cohort of patients with NSCLC with oncogenic driver mutations, including a higher percentage of women and never-smokers. 6,[13][14][15][16][17][18][19] Median cohort PFS was 4.7 (95% CI: 2.3-7.4) months. Median OS was 16.2 (95% CI: 12.0-24.0) months.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Anti–PD-1 Immunotherapy in Patients With Advanced NSCLC With BRAF, HER2, or MET Mutations or RET Translocation: GFPC 01-2018

Guisier

Dubos-Arvis

Viñas

et al. 2020

Journal of Thoracic Oncology

Self Cite

188

150

View full text Add to dashboard Cite

Introduction: Immune-checkpoint inhibitor (ICI) efficacy in patients with NSCLC harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against BRAF-, HER2-, MET-, and RET-NSCLC in a real-world setting.Methods: In this retrospective, multicenter study in ICItreated BRAF-, HER2-, MET-or RET-NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, progression-free survival (PFS), objective response rate, duration of response, and overall survival (OS).Results: There were 107 patients with NSCLC (mean age, 65.5 y) included from 21 centers: 37% were neversmokers, 54% were men, and 93% had adenocarcinoma. Among them, 44 had BRAF mutation (V600: 26), 23 had HER2 mutation, 30 had MET mutation, and nine had RET translocation. Programmed cell death ligand 1 (PD-L1) status was known for 70 patients and was greater than or equal to 1% in 34 patients. Before ICI, patients had received a median of one treatment line. Median duration of response, PFS, and OS were 15.4 (95% confidence interval [CI]: 12.6-not reached [NR]) months, 4.7 (95% CI: 2.3-7.4) months, and 16.2 (95% CI: 12.0-24.0) months, respectively, for the entire cohort. The response rates for BRAF-V600, BRAF-non-V600, HER2, MET, and RET-altered NSCLC were 26%, 35%, 27%, 36%, and 38%, respectively. For patients who were PD-L1 negative and those who were PD-L1 positive, PFS was 3.0 (95% CI: 1.2-NR) and 4.3 (95% CI: 2.1-8.5) months, respectively, and OS was 11.7 (95% CI: 4.1-NR) and 35.8 (95% CI: 9.0-35.2) months, respectively. Toxicities were reported in 28 patients (26%), including 11 patients (10%) with a grade greater than or equal to three. Conclusions:In this real-world setting, ICI efficacy against patients with BRAF-, HER2-, MET-, or RET-NSCLC seemed close to that observed in unselected patients with NSCLC. Large prospective studies on these subsets of patients are needed.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Anti–PD-1 Immunotherapy in Patients With Advanced NSCLC With BRAF, HER2, or MET Mutations or RET Translocation: GFPC 01-2018

Guisier

Dubos-Arvis

Viñas

et al. 2020

Journal of Thoracic Oncology

Self Cite

188

150

View full text Add to dashboard Cite

show abstract

“…Alongside innate inflammatory cells, tumour-infiltrating lymphocytes also play key roles in the tumour microenvironment [13][14][15]. Furthermore, recent advances in immunotherapy have revolutionized cancer treatment by promoting the adaptive immune response against cancer cells [239,240].…”

Section: Future Perspectivesmentioning

confidence: 99%

“…To do so, we make comparisons with studies of inflammation within early mouse neoplastic lesions where available, and also draw upon studies of tumour-associated macrophages (TAMs) and tumour-associated neutrophils (TANs) in the later stages of mammalian cancer. Whilst tumour infiltrating lymphocytes are also key components of the tumour microenvironment in mammalian cancer [13][14][15], there is little evidence that lymphocytes play a role during tumour initiation. The role of lymphocytes during pre-neoplastic development is also yet to be explored in zebrafish cancer models, largely because mature lymphocyte subsets have only recently been characterized in zebrafish.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Elliot

Myllymäki

Feng

2020

Cells

View full text Add to dashboard Cite

The zebrafish is now an important model organism for cancer biology studies and provides unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level, providing novel insights into our understanding of cancer. Here we summarise the available transgenic zebrafish tumour models and discuss what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response towards transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour-associated macrophages and neutrophils in mammalian models and present evidence that supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to the signals that mediate leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells in zebrafish appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

show abstract

“…Following activation by antigen-presenting cells and recognition of specific MHC-I-peptide complexes by the TCR, naive CD8 + T cells in conjunction with costimulatory signaling are activated and differentiate into cytotoxic effector T cells that are then able to target and destroy cells (e.g., infected cells, cancer cells) and secrete cytokines [17]. In addition, the CD8 T cells can also be activated by the Th1 cells via the secretion of IL-2 and other stimulatory molecules [18]. CTL antitumor activity is often referred to as being either direct or indirect.…”

Section: Cd4 and Cd8 T Cellsmentioning

confidence: 99%

Regulation of T Cells in Cancer by Nitric Oxide

Navasardyan

Bonavida

2021

Cells

View full text Add to dashboard Cite

The T cell-mediated immune response is primarily involved in the fight against infectious diseases and cancer and its underlying mechanisms are complex. The anti-tumor T cell response is regulated by various T cell subsets and other cells and tissues in the tumor microenvironment (TME). Various mechanisms are involved in the regulation of these various effector cells. One mechanism is the iNOS/.NO that has been reported to be intimately involved in the regulation and differentiation of the various cells that regulate the anti-tumor CD8 T cells. Both endogenous and exogenous .NO are implicated in this regulation. Importantly, the exposure of T cells to .NO had different effects on the immune response, depending on the .NO concentration and time of exposure. For instance, iNOS in T cells regulates activation-induced cell death and inhibits Treg induction. Effector CD8 T cells exposed to .NO result in the upregulation of death receptors and enhance their anti-tumor cytotoxic activity. .NO-Tregs suppress CD4 Th17 cells and their differentiation. Myeloid-derived suppressor cells (MDSCs) expressing iNOS inhibit T cell functions via .NO and inhibit anti-tumor CD8 T cells. Therefore, both .NO donors and .NO inhibitors are potential therapeutics tailored to specific target cells that regulate the T cell effector anti-tumor response.

show abstract

Janus or Hydra: The Many Faces of T Helper Cells in the Human Tumour Microenvironment

Cited by 10 publications

References 168 publications

Efficacy and Safety of Anti–PD-1 Immunotherapy in Patients With Advanced NSCLC With BRAF, HER2, or MET Mutations or RET Translocation: GFPC 01-2018

Efficacy and Safety of Anti–PD-1 Immunotherapy in Patients With Advanced NSCLC With BRAF, HER2, or MET Mutations or RET Translocation: GFPC 01-2018

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Regulation of T Cells in Cancer by Nitric Oxide

Contact Info

Product

Resources

About