CD4+ T-cell Immunity in the Peripheral Blood Correlates with Response to Anti-PD-1 Therapy

Kagamu, Hiroshi; Kitano, Shigehisa; Yamaguchi, Ou; Yoshimura, Kiyoto; Horimoto, Katsuhisa; Kitazawa, Masashi; Fukui, Kazuhiko; Shiono, Ayako; Mouri, Atsuhito; Nishihara, Fuyumi; Miura, Yu; Hashimoto, Kosuke; Murayama, Yoshitake; Kaira, Kyoichi; Kobayashi, Kunihiko

doi:10.1158/2326-6066.cir-19-0574

Cited by 185 publications

(192 citation statements)

References 40 publications

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“…Moreover, highly differentiated CD4 T cells corresponded to both central and effector memory cells but not to senescent or exhausted cells. Our results were also in very close agreement by a detailed and complete study carried out by Kagamu et al These authors used mass cytometry and found that NSCLC patients responding to nivolumab had a significantly higher percentage of CD62L low CD4 T cells than non-responders at baseline [34]. Interestingly, these T cells were also double negative in CD27 and CD28, and corresponded to memory subsets.…”

Section: Cd4 T Cellssupporting

confidence: 90%

“…Tregs promote immunosuppression and tolerance once infiltrated into the TME. Accordingly, a decrease in peripheral blood Tregs after ipilimumab treatment in metastatic melanoma patients was associated to disease control and OS [36], while the baseline percentage of CD25 + FoxP3 + CD4 T cells in NSCLC patients treated with nivolumab was higher in non-responders [34]. These results overall suggest that a decrease of this immunosuppressive population contributes to the efficacy of ICI therapies.…”

Section: Cd4 T Cellsmentioning

confidence: 72%

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Systemic Blood Immune Cell Populations as Biomarkers for the Outcome of Immune Checkpoint Inhibitor Therapies

Hernández

Arasanz

Chocarro

et al. 2020

IJMS

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The development of cancer immunotherapy in the last decade has followed a vertiginous rhythm. Nowadays, immune checkpoint inhibitors (ICI) which include anti-CTLA4, anti-PD-1 and anti-PD-L1 antibodies are in clinical use for the treatment of numerous cancers. However, approximately only a third of the patients benefit from ICI therapies. Many efforts have been made for the identification of biomarkers allowing patient stratification into potential responders and progressors before the start of ICI therapies or for monitoring responses during treatment. While much attention is centered on biomarkers from the tumor microenvironment, in many cases biopsies are not available. The identification of systemic immune cell subsets that correlate with responses could provide promising biomarkers. Some of them have been reported to influence the response to ICI therapies, such as proliferation and activation status of CD8 and CD4 T cells, the expression of immune checkpoints in peripheral blood cells and the relative numbers of immunosuppressive cells such as regulatory T cells and myeloid-derived suppressor cells. In addition, the profile of soluble factors in plasma samples could be associated to response or tumor progression. Here we will review the cellular subsets associated to response or progression in different studies and discuss their accuracy in diagnosis.

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Section: Cd4 T Cellssupporting

confidence: 90%

Section: Cd4 T Cellsmentioning

confidence: 72%

Systemic Blood Immune Cell Populations as Biomarkers for the Outcome of Immune Checkpoint Inhibitor Therapies

Hernández

Arasanz

Chocarro

et al. 2020

IJMS

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“…These results highlighted the up-regulation of LAG-3 as a major escape mechanism to PD-1/PD-L1 monoblockade strategies. Very similar results were obtained in two other independent studies by Kagamu and collaborators, and Julia and collaborators (Julia et al, 2019;Kagamu et al, 2020). In the study by Zuazo et al responders had a high percentage of highly differentiated CD27 − CD28 − memory CD4 T cells before starting immunotherapies, and could be used as a predictive biomarker.…”

Section: Tumor-extrinsic Factors and Resistance To Pd-l1/pd-1 Blockadsupporting

confidence: 79%

“…The first study correlated the high baseline frequency of central memory CD4 T cells with response to immunotherapy in NSCLC and renal cancer patients using flow cytometry (Julia et al, 2019). In the second study, NSCLC patients with high baseline percentages of CD62L low effector CD4 T cells quantified by CyTOF had a high chance of responding to PD-L1/PD-1 blockade (Kagamu et al, 2020). The dynamics and behavior of these CD4 T cell subsets were identical to those from highly-differentiated memory CD4 T cells in our study, strongly suggesting that we were all monitoring the same CD4 T cell subsets but with different markers.…”

Section: Discussionmentioning

confidence: 99%

Resistance to PD-L1/PD-1 Blockade Immunotherapy. A Tumor-Intrinsic or Tumor-Extrinsic Phenomenon?

et al. 2020

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Cancer immunotherapies targeting immune checkpoints such as programmed cell-death protein 1 (PD-1) and its ligand programmed cell-death 1 ligand 1 (PD-L1), are revolutionizing cancer treatment and transforming the practice of medical oncology. However, despite all the recent successes of this type of immunotherapies, most patients are still refractory and present either intrinsic resistance or acquired resistance. Either way, this is a major clinical problem and one of the most significant challenges in oncology. Therefore, the identification of biomarkers to predict clinical responses or for patient stratification by probability of response has become a clinical necessity. However, the mechanisms leading to PD-L1/PD-1 blockade resistance are still poorly understood. A deeper understanding of the basic mechanisms underlying resistance to cancer immunotherapies will provide insight for further development of novel strategies designed to overcome resistance and treatment failure. Here we discuss some of the major molecular mechanisms of resistance to PD-L1/PD-1 immune checkpoint blockade and argue whether tumor intrinsic or extrinsic factors constitute main determinants of response and resistance.

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“…Some, such as increases in the frequency of immunosuppressive cells like CD4+ regulatory T-cells (T-regs), are associated with a worse prognosis 11 . Other changes, such as altered T-cell differentiation status, are associated with increased clinical response after immunotherapy 12 . NK cells in adult cancer patients are unaltered in frequency but are less cytotoxic 13 , 14 , 15 , 16 .…”

Section: Introductionmentioning

confidence: 99%

Age related defects in NK cell immunity revealed by deep immune profiling of pediatric cancer patients

Syrimi

Khan

Murray

et al. 2020

Preprint

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Syrimi et al. High-Dimensional mass cytometry analysis reveals systemic immune perturbations in paediatric cancer influenced by ageOne Sentence Summary: High dimensional analysis of systemic immunity in pediatric cancer patients reveals clinically relevant immune changes in NK and T-cells that vary with patient age. Abstract:Systemic immunity plays important roles in cancer immune surveillance and therapy but little is known about the immune status of healthy children or children with cancer. We performed a high dimensional single cell analysis of systemic immunity in pediatric cancer patients and agematched healthy children. In young children with cancer (age <8years) NK cells were decreased in frequency, maturity, expression of perforin and granzyme-B, and were less cytotoxic in ex vivo assays. NK cell activity was restored after in vitro culture with interleukin-2. In contrast, older children with cancer (>8 years old) had decreased naive CD4 and CD8 T-cells with concomitant increases in effector memory and T effector memory RA-revertant (TEMRA) Tcells. These immunological changes in pediatric cancer patients are relevant to the better understanding of how cancers diagnosed in childhood interact with systemic immunity and could inform the development and application of effective immune-modulating therapies in the pediatric population. Syrimi et al. High-Dimensional mass cytometry analysis reveals systemic immune perturbations in paediatric cancer influenced by age

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CD4+ T-cell Immunity in the Peripheral Blood Correlates with Response to Anti-PD-1 Therapy

Cited by 185 publications

References 40 publications

Systemic Blood Immune Cell Populations as Biomarkers for the Outcome of Immune Checkpoint Inhibitor Therapies

Systemic Blood Immune Cell Populations as Biomarkers for the Outcome of Immune Checkpoint Inhibitor Therapies

Resistance to PD-L1/PD-1 Blockade Immunotherapy. A Tumor-Intrinsic or Tumor-Extrinsic Phenomenon?

Age related defects in NK cell immunity revealed by deep immune profiling of pediatric cancer patients

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