Cancer Immunotherapy Review
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Bristol-Myers Squibb's Nivolumab can cure Hodgkin's Lymphomia - The Hoops News

Bristol-Myers Squibb's Nivolumab can cure Hodgkin's Lymphomia - The Hoops News | Cancer Immunotherapy Review | Scoop.it
A promising new drug shows signs of reducing tumors caused by the cancer Hodgkins lymphomia.
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A magic life saving cure for advanced metastatic melanoma.  
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Ipilimumab (BMS) Review: A Cancer Breakthrough? - un knol de Krishan Maggon

Ipilimumab (BMS) Review: A Cancer Breakthrough? - un knol de Krishan Maggon | Cancer Immunotherapy Review | Scoop.it
FDA has approved Yervoy (ipilimumab, BMS) under REMS for the treatment of metastatic melanoma. The European expert panel CHMP...
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rosywills's comment, September 22, 2017 4:07 AM
Cancer Immunotherapy Market is expected to reach USD 119.39 Billion by 2021
Download Free Brochure @ http://bit.ly/2cHlrFH
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Mini-tumours turn immune cells into cancer fighters : Research Highlights

Mini-tumours turn immune cells into cancer fighters : Research Highlights | Cancer Immunotherapy Review | Scoop.it
Miniature tumours in a dish can be used to give immune cells cancer-killing powers — and might illuminate why some tumours resist a promising therapy.
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EMA and FDA prune the checkpoint inhibitor treatment landscape

EMA and FDA prune the checkpoint inhibitor treatment landscape | Cancer Immunotherapy Review | Scoop.it
The European Medicines Agency (EMA) and FDA have recently restricted the indications for first-line pembrolizumab and atezolizumab to patients with programmed cell death 1 ligand 1 (PD-L1)-high advanced urothelial carcinoma, a decision made following interim analyses from the ongoing Keynote-361 and IMvigor130 phase III trials. Questions remain on the magnitude of inferior survival and standardized implementation of PD-L1 testing.
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Rosenberg named co-recipient of 2018 Albany Prize

Rosenberg named co-recipient of 2018 Albany Prize | Cancer Immunotherapy Review | Scoop.it
NCI’s Steven A. Rosenberg, M.D., Ph.D., has been named a recipient of the 2018 Albany Medical Center Prize in Medicine and Biomedical Research for his pioneering immunotherapy research. He will share the prize with two NCI-supported immunotherapy researchers.
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Trailblazing Researchers (Drs James Allison, Carl June and Steven Rosenberg) in Immunotherapy Selected to Receive Americas Most Distinguished Prize in Medicine

Trailblazing Researchers (Drs James Allison, Carl June and Steven Rosenberg) in Immunotherapy Selected to Receive Americas Most Distinguished Prize in Medicine | Cancer Immunotherapy Review | Scoop.it
Trailblazing Researchers in Immunotherapy Selected to Receive Americas Most Distinguished Prize in Medicine.

 

Three visionary scientists whose work has led to a revolutionary new way to treat cancer and other diseases have been announced as the recipients of the 2018 Albany Medical Center Prize in Medicine and Biomedical Research. Their insights into the immune system and their work on what is known as immunotherapy have led to innovative new drugs for cancer, HIV and other diseases, with many already saving and extending the lives of tens of thousands of patients. The awardees are:

 

  • James P. Allison, Ph.D., The University of Texas MD Anderson Cancer Center

 

  • Carl June, M.D., Perelman School of Medicine, University of Pennsylvania

 

  • Steven A. Rosenberg, M.D., Ph.D., National Cancer Institute, National Institutes of Health

 

The $500,000 award has been given annually since 2001 to those who have altered the course of medical research and is one of the largest prizes in medicine and science in the United States. It will be awarded on Wednesday, Sept. 26 during a celebration in Albany, New York.

The awardees were chosen to receive the 2018 Albany Prize for their groundbreaking research in immunology, the translation of their ideas into clinically meaningful therapies for diseases, including metastatic melanoma, lung cancer and leukemia, and their leadership in moving the field of immunotherapy forward.

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Nektar Immuno-Oncology R&D NKTR-214 (CD122-agonist)

Nektar Immuno-Oncology R&D NKTR-214 (CD122-agonist) | Cancer Immunotherapy Review | Scoop.it

 

NKTR-214 is a CD122-biased agonist designed to stimulate the patient's own immune system to fight cancer. NKTR-214 is designed to grow specific cancer-killing T cells and natural killer (NK) cell populations in the body which fight cancer, which are known as endogenous tumor-infiltrating lymphocytes (TILs). NKTR-214 stimulates these cancer-killing immune cells in the body by targeting CD122 specific receptors found on the surface of these immune cells, known as CD8+ effector T cells and Natural Killer (NK) cells. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these effector T cells.1 In clinical and preclinical studies, treatment with NKTR-214 resulted in expansion of these cells and mobilization into the tumor micro-environment.2,3NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

 

 

In April 2018, Nektar announced a new clinical collaboration agreement with Takeda to evaluate NKTR-214 in combination with TAK-659, a dual SYK and FLT-3 inhibitor in liquid and solid tumors with the first of these studies expected to begin in the second half of 2018 in patients with Non-Hodgkin Lymphoma. 

 

In May 2018, Nektar announced a clinical collaboration with Syndax Pharmaceuticals to evaluate NKTR-214 in combination with entinostat, an oral, small molecule Class 1 specific HDAC inhibitor, in patients with metastatic melanoma who have previously progressed on treatment with an anti-PD-1 agent.

Krishan Maggon 's insight:

NKTR 214 is in Phase II trials with BMS Nivolumab.

 

In February 2018, Nektar and Bristol-Myers Squibb entered into a global development and commercialization agreement to evaluate the full potential of NKTR-214 plus Opdivo® (nivolumab) in more than 20 indications in 9 tumor types including melanoma, renal cell carcinoma, non-small cell lung cancer, bladder and triple negative breast cancer.

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Exosomes from Cancer Cells Could Predict Immunotherapy Responses

Exosomes from Cancer Cells Could Predict Immunotherapy Responses | Cancer Immunotherapy Review | Scoop.it
Cancer Cells’ Immune-Evasion Mechanism may help explain the considerable differences in patients’ responses to immunotherapy treatment.
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Pan-cancer deconvolution of tumour composition using DNA methylation

Pan-cancer deconvolution of tumour composition using DNA methylation | Cancer Immunotherapy Review | Scoop.it
The nature and extent of immune cell infiltration into solid tumours are key determinants of therapeutic response. Here, using a DNA methylation-based approach to tumour cell fraction deconvolution, we report the integrated analysis of tumour composition and genomics across a wide spectrum of solid cancers. Initially studying head and neck squamous cell carcinoma, we identify two distinct tumour subgroups: ‘immune hot’ and ‘immune cold’, which display differing prognosis, mutation burden, cytokine signalling, cytolytic activity and oncogenic driver events. We demonstrate the existence of such tumour subgroups pan-cancer, link clonal-neoantigen burden to cytotoxic T-lymphocyte infiltration, and show that transcriptional signatures of hot tumours are selectively engaged in immunotherapy responders. We also find that treatment-naive hot tumours are markedly enriched for known immune-resistance genomic alterations, potentially explaining the heterogeneity of immunotherapy response and prognosis seen within this group. Finally, we define a catalogue of mediators of active antitumour immunity, deriving candidate biomarkers and potential targets for precision immunotherapy.
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Tumor cells can unleash tiny weapons to ward off immune system attacks

Tumor cells can unleash tiny weapons to ward off immune system attacks | Cancer Immunotherapy Review | Scoop.it
A new study points to the weapons, or exosomes, as a potential biomarker to predict which patients might respond to anti-PD-1 therapies.
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 Cancer Immunology Research

 Cancer Immunology Research | Cancer Immunotherapy Review | Scoop.it
Sign up for Table of Contents Alerts! Be the first to know. 1 2 3 From the Current Issue What We're Reading Cancer Immunol Res August 1 2018 6 (8) 881-881; Research Articles Julie M. Diamond, Claire Vanpouille-Box, Sheila Spada, Nils-Petter Rudqvist, Jessica R. Chapman, Beatrix M. Ueberheide, Karsten A. Pilones, Yasmeen Sarfraz, Silvia C. Formenti and Sandra Demaria Cancer Immunol Res August 1 2018 6 (8) 910-920; DOI:10.1158/2326-6066.CIR-17-0581 Irradiated tumor-derived exosomes were shown to contain dsDNA that, when transported to DCs, induced upregulation of costimulatory molecules and IFN-I responses. In vivo, vaccination with the irradiated tumor-derived exosomes reduced tumor growth and induced potent CD8+ T-cell responses. Research Articles Valeria Schinzari, Eleonora Timperi, Giulia Pecora, Francesco Palmucci, Daniela Gallerano, Alessio Grimaldi, Daniela Angela Covino, Nicola Guglielmo, Fabio Melandro, Emy Manzi, Andrea Sagnotta, Francesco Lancellotti, Luca Sacco, Piero Chirletti, Gian Luca Grazi, Massimo Rossi and Vincenzo Barnaba Cancer Immunol Res August 1 2018 6 (8) 941-952; DOI:10.1158/2326-6066.CIR-17-0712 The Wnt3a/β-catenin pathway supports a protumor environment. Secreted Wnt3a was found to be overexpressed in human colorectal and hepatocellular carcinomas, interfere with naïve and effector T-cell differentiation, and affect the function of infiltrating T cells. Research Articles Ilenia Pacella, Ilenia Cammarata, Chiara Focaccetti, Stefano Miacci, Alessandro Gulino, Claudio Tripodo, Micol Ravà, Vincenzo Barnaba and Silvia Piconese Cancer Immunol Res August 1 2018 6 (8) 953-964; DOI:10.1158/2326-6066.CIR-17-0713 The Wnt3a/β-catenin pathways modulate antitumor T-cell responses. In a mouse tumor model, administration of an anti-Wnt3a neutralizing antibody-controlled tumor growth by reshaping signals in the tumor microenvironment. OnlineFirst Articles Cellular cytotoxicity of CD20 monoclonal antibodies Karl R VanDerMeid, et al. CD30.CAR T cells target EC via Fas/FasL interaction Lee Kyung Hong, et al. JQ1 amplifies PD-1 blockade in Kras-mutant NSCLC Dennis O Adeegbe, et al. DCs Present Tumor Microparticle Antigens to CD8+ T Cells Jingwei Ma, et al. Load more
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γδ T cells control humoral immune response by inducing T follicular helper cell differentiation

γδ T cells control humoral immune response by inducing T follicular helper cell differentiation | Cancer Immunotherapy Review | Scoop.it
Many immune functions have been reported for γδ T cells, including the regulation of antibody responses. Here the authors show that CXCR5+ γδ T cells release Wnt ligands to initiate the T follicular helper cell differentiation program and promote antibody production.
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Challenges and perspectives in the immunotherapy of Hodgkin lymphoma - ScienceDirect

Challenges and perspectives in the immunotherapy of Hodgkin lymphoma - ScienceDirect | Cancer Immunotherapy Review | Scoop.it
The microenvironment of Hodgkin lymphoma appears to be unique in the field of human disease: the malignant Reed-Sternberg cells only constitute 1% of the cells in the lymphoma, but they are surrounded by an extensive immune infiltrate. Reed-Sternberg cells exhibit 9p24.1/PD-L1/PD-L2 copy number alterations and genetic rearrangements associated with programmed cell death ligand 1/ ligand 2 (PD-L1/2) overexpression, together with major histocompatibility complex-I (MHC-I) and major histocompatibility complex-II (MHC-II) downregulation (which may facilitate the tumour's immune evasion). Although HL may be a situation in which defective immune surveillance is restored by anti-PD1 therapy, it challenges our current explanation of how anti-PD1 agents work because MHC-I expression is required for CD8-T-cell-mediated tumour antigen recognition. Here, we review recent attempts to understand the defects in immune recognition in HL and to design an optimal evidence-based treatment for combination with anti-PD1.

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TCR signal strength controls the differentiation of CD4+ effector and memory T cells

TCR signal strength controls the differentiation of CD4+ effector and memory T cells | Cancer Immunotherapy Review | Scoop.it
T cell differentiation into effector and memory T cell subsets is influenced by T cell receptor (TCR) signals. Snook et al . examine how TCR signals influence CD4+ T cell differentiation using a panel of cloned TCRs that recognize the same MHC II–restricted epitope of lymphocytic choriomeningitis virus. Strong TCR signals were associated with TH1 differentiation, whereas lower TCR signal strength corresponded with follicular helper T cell and memory T cell differentiation. Low CD25 expression by early effector T cells also predicted memory differentiation, although CD25 expression levels were not predictive of recall responses. Enhanced TCR signaling via knockdown of SHP-1 favored TH1 over Tfh and memory T cell differentiation. These results indicated that stronger TCR signaling promotes terminal effector TH1 differentiation.

CD4+ T cell responses are composed of heterogeneous T cell receptor (TCR) signals that influence the acquisition of effector and memory characteristics. We sought to define early TCR-dependent activation events that control T cell differentiation. A polyclonal panel of TCRs specific for the same viral antigen demonstrated substantial variability in TCR signal strength, expression of CD25, and activation of nuclear factor of activated T cells and nuclear factor κB. After viral infection, strong TCR signals corresponded to T helper cell (TH1) differentiation, whereas T follicular helper cell and memory T cell differentiation were most efficient when TCR signals were comparatively lower. We observed substantial heterogeneity in TCR-dependent CD25 expression in vivo, and the vast majority of CD4+ memory T cells were derived from CD25lo effector cells that displayed decreased TCR signaling in vivo. Nevertheless, memory T cells derived from either CD25lo or CD25hi effector cells responded vigorously to rechallenge, indicating that, although early clonal differences in CD25 expression predicted memory T cell numbers, they did not predict memory T cell function on a per cell basis. Gene transcription analysis demonstrated expression clustering based on CD25 expression and enrichment of transcripts associated with enhanced T follicular helper cell and memory development within CD25lo effector cells. Direct enhancement of TCR signaling via knockdown of Src homology region 2 domain–containing phosphatase 1, a tyrosine phosphatase that suppresses early TCR signaling events, favored the differentiation of TH1 effector and memory cells. We conclude that strong TCR signals during early T cell activation favor terminal TH1 differentiation over long-term TH1 and T follicular helper cell memory responses.
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National Coverage Analysis of CAR-T Therapies — Policy, Evidence, and Payment | NEJM

National Coverage Analysis of CAR-T Therapies — Policy, Evidence, and Payment | NEJM | Cancer Immunotherapy Review | Scoop.it
Perspective from The New England Journal of Medicine — National Coverage Analysis of CAR-T Therapies — Policy, Evidence, and Payment...

 

In a trial involving 101 patients with non-Hodgkin’s lymphoma, axicabtagene ciloleucel produced complete remission in 51, which led to its approval by the Food and Drug Administration (FDA). Tisagenlecleucel (Kymriah, Novartis), another anti-CD19 CAR-T therapy, led to complete responses in 22 of 69 patients (32%). Juno Therapeutics also has a development program for anti–CD19 CAR-T therapies. (I have been involved in various ways with all three manufacturers.)

The two approved CAR-T therapies have boxed warnings regarding serious side effects, and each costs about $400,000. Ancillary costs include initial leukapheresis and inpatient stays that may be necessitated by frequent treatment complications, which may result in administration of tocilizumab (up to four doses at $2,500 per dose). Hernandez and colleagues estimate that these ancillary costs would average around $33,000 per patient; media reports suggest a figure 10 times as high.

 

CAR-T therapies have broken new ground on many fronts — they have shown efficacy in patients who previously had few options, but they cost multiple times what any previously approved cancer therapy costs. Their rapid approval based on small, uncontrolled studies reflects their promise. But they are no panacea. Ms. Kearney died a few weeks after receiving her dose of the CAR-T therapy that cost nearly $400,000, and she endured an extended hospital and ICU stay along the way. She told WBUR reporter Richard Knox that she knew death was a possible outcome, and she was grateful for the chance to receive a possibly effective treatment — a reminder of what’s at stake for Medicare patients when CMS considers CAR-T therapy coverage. If Medicare chooses to cover this therapy, it should think carefully about how to do it.

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HTG EdgeSeq Immuno-Oncology Assay

HTG EdgeSeq Immuno-Oncology Assay | Cancer Immunotherapy Review | Scoop.it
The HTG EdgeSeq Immuno-Oncology Assay (I/O) quantitatively measures the expression of 549 human RNA transcripts believed to be involved in the innate and adaptive immune response to cancer.
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Cross-talk between T Cells and Hematopoietic Stem Cells during Adoptive Cellular Therapy for Malignant Glioma

Cross-talk between T Cells and Hematopoietic Stem Cells during Adoptive Cellular Therapy for Malignant Glioma | Cancer Immunotherapy Review | Scoop.it
Purpose: Adoptive T-cell immunotherapy (ACT) has emerged as a viable therapeutic for peripheral and central nervous system (CNS) tumors. In peripheral cancers, optimal efficacy of ACT is reliant on dendritic cells (DCs) in the tumor microenvironment.
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1392 Genes in a single reaction: HTG EdgeSeq Precision Immuno-Oncology Panel

1392 Genes in a single reaction: HTG EdgeSeq Precision Immuno-Oncology Panel | Cancer Immunotherapy Review | Scoop.it
The HTG EdgeSeq Precision Immuno-Oncology Panel interrogates 1392 genes in a single reaction from FFPE tissue and PAXGene samples to categorize and sub-type tumors based on previously defined molecular expression phenotypes all with a single assay.
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A radiomics approach to assess tumour-infiltrating CD8 cells and response to anti-PD-1 or anti-PD-L1 immunotherapy: an imaging biomarker, retrospective multicohort study

A radiomics approach to assess tumour-infiltrating CD8 cells and response to anti-PD-1 or anti-PD-L1 immunotherapy: an imaging biomarker, retrospective multicohort study | Cancer Immunotherapy Review | Scoop.it
The radiomic signature of CD8 cells was validated in three independent cohorts. This
imaging predictor provided a promising way to predict the immune phenotype of tumours
and to infer clinical outcomes for patients with cancer who had been treated with
anti-PD-1 and PD-L1.
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Association of Acute Interstitial Nephritis With Programmed Cell Death 1 Inhibitor Therapy in Lung Cancer Patients

Association of Acute Interstitial Nephritis With Programmed Cell Death 1 Inhibitor Therapy in Lung Cancer Patients | Cancer Immunotherapy Review | Scoop.it
Immune checkpoint inhibitors that target the programmed death 1 (PD-1) signaling pathway
have recently been approved for use in advanced pretreated non–small cell lung cancer
and melanoma. Clinical trial data suggest that these drugs may have adverse effects on the kidney, but these effects have...
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Biomaterial-assisted targeted modulation of immune cells in cancer treatment

Biomaterial-assisted targeted modulation of immune cells in cancer treatment | Cancer Immunotherapy Review | Scoop.it
Immunotherapies have shown significant promise in cancer treatment. This Review discusses how a range of materials have been employed to enhance the effectiveness of these therapies by mediating their delivery and immunomodulatory activity.
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Combined local and systemic attacks

Combined local and systemic attacks | Cancer Immunotherapy Review | Scoop.it
Intratumoral injection of a hydrogel impregnated with radioisotope-labelled catalase and an immunostimulant, along with systemic immune checkpoint blockade, inhibits tumour growth in mouse models of localized cancer and metastatic cancer.
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Immuno Oncology Summit

Immuno Oncology Summit | Cancer Immunotherapy Review | Scoop.it
Join over 600 thought leaders at industry’s leading Immuno-Oncology event and learn about the latest research in a comprehensive 12-track program, network and build lasting collaborations with an international mix of delegates from industry and academia, and gain actionable solutions to drive your...
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JCI - Emerging strategies for combination checkpoint modulators in cancer immunotherapy

JCI - Emerging strategies for combination checkpoint modulators in cancer immunotherapy | Cancer Immunotherapy Review | Scoop.it
Current immune checkpoint-modulating agents have demonstrated clinical efficacy in certain tumor types, particularly those with a high burden of tumor-specific neoantigens, high tumor-mutational burden, and abundant tumor-infiltrating T cells. However, these tumors often stop responding, with signs of T cells exhaustion, decreased T cell effector function, and upregulated inhibitory checkpoints. To enhance antitumor immunity and rescue exhausted T cells, newer inhibitory and stimulatory checkpoint modulators are being tested as monotherapy or in combination with approved checkpoint inhibitors. In contrast, tumors with low tumor-mutational burden, low neoantigen burden, and a paucity of T cells are immunologically “cold,” and therefore first require the addition of agents to facilitate the induction of T cells into tumors. Cold tumors also often recruit immunosuppressive cell subsets, including regulatory T cells, myeloid-derived suppressor cells, and macrophages, and secrete immunosuppressive soluble cytokines, chemokines, and metabolites. To unleash an optimal antitumor immune response, combinatorial therapeutics that combine immune checkpoints with other modalities, such as vaccines, are being developed. From current preclinical data, it appears that combinatorial strategies will provide robust and durable responses in patients with immunologically cold cancers.
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Hidden signs in cancer tissue | EurekAlert! Science News

Hidden signs in cancer tissue | EurekAlert! Science News | Cancer Immunotherapy Review | Scoop.it
When scientists at ETH Zurich analysed huge amounts of genetic cancer data, they found previously unresearched molecular changes. These could help in developing new personalised cancer treatments.
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PD-1 Controls Follicular T Helper Cell Positioning and Function

PD-1 Controls Follicular T Helper Cell Positioning and Function | Cancer Immunotherapy Review | Scoop.it
Summary
Follicular T helper (Tfh) cells highly express the programmed cell death-1 (PD-1) molecule. Whereas inhibition of T cell receptor (TCR) signaling and CD28 co-stimulation is thought to be the primary mode of PD-1 functions, whether and how PD-1 regulates Tfh cell development and function is unclear. Here we showed that, when engaged by the ensemble of bystander B cells constitutively expressing PD-1 ligand 1 (PD-L1), PD-1 inhibited T cell recruitment into the follicle. This inhibition involved suppression of PI3K activities downstream of the follicle-guidance receptor CXCR5, was independent of co-signaling with the TCR, and necessitated ICOS signaling to overcome. PD-1 further restricted CXCR3 upregulation on Tfh cells, serving to concentrate these cells toward the germinal center territory, where PD-L1-PD-1 interactions between individual Tfh and B cells optimized B cell competition and affinity maturation. Therefore, operating in both costimulation-independent and -dependent manners, PD-1 controls tissue positioning and function of Tfh cells.
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New Cancer Drugs Rally the Body’s Troops But They Should Not Be Immune to Criticism | Office for Science and Society - McGill University

New Cancer Drugs Rally the Body’s Troops But They Should Not Be Immune to Criticism | Office for Science and Society - McGill University | Cancer Immunotherapy Review | Scoop.it
Take-home message “Cancer immunotherapy” means waking up your immune system so it can see and kill your cancer Some of these therapies have had moderate success, but they are very expensive, do not work for everyone, and can cause diseases like arthritis and inflammation of the large intestine ...
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