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Cancer Immunotherapy - Growing focus on CD4+ T lymphocytes and MHC Class II Neoantigens

Posted by Anthony G Pietrantoni on Feb 11, 2020 1:00:00 PM

It is now well accepted that CD8+ T cells play a central role in mediating anti-tumor immunity by recognizing tumor-associated antigens presented on major histocompatibility complex class I by their expressed T cell receptor.  Majority of studies on cancer neoantigens have therefore focused on MHC class I restricted antigens recognized by CD8+ T cells.   However it is also becoming increasingly clear that CD8+ T cell binding neoantigens are not sufficient for mounting a powerful anti tumor response. The recent paper by Alspach et al. proved that spontaneous and immunotherapy-induced antitumor responses required presence of CD4+ in addition to CD8+ T cells (1).

Multiple studies indicate that CD4+ T cells mediate antitumor effects through mechanisms that vary according to tumor environments whether they act as helper or cytotoxic cells but are ultimately dependent on MHC class II neoantigens.   In some instances CD4+ T cells were shown to acquire cytotoxicity activity in vivo in presence of a high level of IL-2 or when IL-2 sequestering T Reg cells were absent (2).  A recent investigation reported that cytotoxic CD4+ T cells are particularly abundant among supercentenarians and reached 25% of T cells on average, suggesting they are essential to protect against infections and cancers, contributing to achieve an extended disease-free life expectancy (3).  Therefore, with improved understanding of the intricate interactions between cytotoxic and helper CD4+ lymphocytes with tumors and antigen presenting cells, interest is currently focused on MHC class II dependent immune activation mechanisms.  MHC class II restricted neoantigens have now the potential to be promising targets of cancer immunotherapies.

Learn more about Class II Tetramers

 

References

(1)Alspach, E. et al. MHC-II neoantigens shape tumour immunity and response to immunotherapy. Nature 574: 696–701 (2019).

(2) Śledzińska, A. et al. Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4+ T Cells. Immunity. 52(1):151-166 (2020).

(3) Hashimoto K. et al. Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians. Proc Natl Acad Sci USA. 116(48):24242-24251 (2019).

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Topics: Tetramer, Cancer

Is your drug candidate able to reverse the T Cell Exhaustion-like state in our in vitro functional screening assay?

Posted by Pirouz Daftarian, Ph.D. on Dec 12, 2019 1:00:00 PM

The goal of cancer immune checkpoint therapies is to cure tumor-specific T cells from dysfunction which is caused by elements from tumor deposits.  In this blog, we briefly describe the process of T cell exhaustion and how it can be harnessed for immuno-oncology drug discovery and more specifically to screen immune checkpoint drug candidates. First, the current function-based characterization methods for immunomodulatory drug candidates will be summarized. We have selected three methods which mimic prerequisite parameters of early T cell exhaustion (TEX). Next, we briefly describe an improved recall antigen-based potency assay as detailed elsewhere. Lastly, we describe an in vitro reversible early TEX-like  model, which may be tailored with cancer-induced T cell suppression agents.  Here it should be noted that cancer induced T cell dysfunction is also referred to as TEX, covering a broad spectrum of different molecular T cell pathologies. The term “T cell exhaustion” in this review mainly refers to an early stage of this process.  We have devised an in vitro model that recapitulates components of tumor deposits responsible for inducing TEX.

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Topics: Tetramer, Cancer, t cell

Why pure exosome isolation matters

Posted by Lise Peeters, PhD on Mar 28, 2017 11:30:00 AM

Exosomes are cell-derived vesicles originating from multi-vesicular bodies and found in biological fluids such as blood, saliva, urine, and breast milk. Sizes of these extracellular vesicles (EVs) range between 30-100 nm. Due to their capacity to transfer proteins, lipids and nucleic acids, exosomes can influence various physiological and pathological functions (Yañez-Mo et al., 2015).

Exosomes play a key role in cell-cell communication and circulate in bloodstream, and therefore, are implicated as a disease biomarker for cancer and immune system disorders. However, there is limited information regarding efficient methods for obtaining pure exosomes. MBL offers a unique exosome purification kit that can help researchers purify exosomes from their sample.

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Topics: Cancer, Exosomes, Liquid Biopsy, Exosome, Biomarker, Purify exosome

Give Your Research 100% With a S100 Antibody

Posted by Deane Buckley on Jul 7, 2015 10:00:00 AM

 

Figure: Schematic representation of S100 proteins in the MAP kinase and NF-kappaB pathways.

S100 proteins are a family of proteins known for their role in a variety of cellular pathways and diseases. This blog post will catch you up on the latest research on these important proteins.

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Topics: Immunology, Apoptosis, Cancer

The Fas and the Furious 2: The Importance of Fas in Cancer

Posted by Deane Buckley on May 13, 2015 3:14:46 PM

 

Given the prominent role of Fas in many important cell functions (7 Facts to Catch You Up to Speed on Fas), Fas has been implicated in a variety of disease states such as cancer. Here are some major findings from recent research about the role of Fas in cancer:

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Topics: Apoptosis, Cancer

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