Breaking news for cancer researchers! We are pleased to have recently added innovative cancer Arrays to our product offer. You might tell me that there are a lot of new cancer arrays every year and it’s not really necessary to write a post about it… but read on and I’m sure you’ll share my enthusiasm!
The role of the interactions between tumor cells and their microenvironment (TME) is now well-established in various stages of cancer development. Cytokines, produced by both the cancer and the immune cells, actively contribute to these critical connections (see the previous posts related to the crosstalk between cancer and immune cells in relation to tumor escape, immunoediting and immunosurveillance).
In a recent review published in BBA, RayBiotech‘s team highlights the “cytokine signatures and dynamics” seen during cancer development. They also demonstrate the necessity of designing relevant multiplex immunoassays for the profiling and the quantification of cytokines in biomarker and anti-cancer drug discovery programs.
Valerie Sloane Jones, Ren-Yu Huang, Li-Pai Chen, Zhe-Sheng Chen, Liwu Fu, Ruo-Pan Huang “Cytokines in cancer drug resistance: Cues to new therapeutic strategies” (2016) Biochimica et Biophysica Acta, Volume 1865, Issue 2, 255–265. DOI:10.1016/j.bbcan.2016.03.005.
Download the publication written by RayBiotech, the leader in planar Antibody Arrays.
Following our series of posts on tumour immunity, I’d like to mention an article published by researchers from the Ben-Gurion University of the Negev (Israel). The authors investigated the negative correlation between caffeine consumption and incidence of tumours. Or to say it more simply, intake of caffeine favours the immune system fighting tumours. (1) [Read more…]
Early in 2015, researchers of The University of Queensland Diamantina Institute (Australia) have shown a very sensible approach to the discovery of new biomarkers associated to transition from non-metastatic tumours to metastatic tumours in osteosarcoma. Not to be a spoiler, but they found that the uPA/uPAR axis is crucial for this, and can be used as a prognostic biomarker. In fact, inhibition of this axis can inhibit the metastasis in this type of tumours. (Endo-Muñoz et al. DOI: 10.1371/journal.pone.0133592).
I don’t want to focus on the biomarker per se, but rather, on the process that this lab followed to discover this new biomarker. [Read more…]
PSA (Prostate Specific Antigen) has been (and still is) the biomarker of choice for the diagnosis and follow up of patients having a Prostate Cancer (PCa). However, even if it has been used for quite some time now, it is not too specific and its levels may be high for other physiological situations, and not only cancer. Therefore, the need for more specific biomarkers for the correct management of PCa patients is mandatory. A recent publication by Heidegger et al. suggests that Eotaxin-1 (CCL11) could be a more specific biomarker. [Read more…]
A ready-to-use E3 ligase activity enzymatic assay, the E3LITE kit, has been recently designed enabling researchers to screen for E3 enzyme inhibitors and potentially new therapeutical drugs. What’s it for and why is it of interest?
Three papers on the role of the TGF-beta pathway in different cancers have recently been published.
It was already known that this pathway is involved in processes such as cell growth, cell differentiation, apoptosis, cellular homeostasis and other cellular functions. The pathway as such works in quite a simple way: [Read more…]
If you are using protein immunoblots, we would like to share with you some recent publications in top-tier journals highlighting the applications of Antibody Arrays for secretome studies. These arrays act as a multiplex western blot, detecting up to 274 proteins in one experiment with high specificity.
So rather than using hundreds of antibodies or ELISAs, or stripping and re-probing blots, you can use Antibody Arrays and compare expression levels of many cytokines, growth factors, receptors, and other proteins in a single assay!. And if you are too busy or prefer experts to take care of your valuable samples, do not hesitate to contact tebu-bio’s laboratory, a certified service provider, for performing your array experiments for Biomarker discovery and Protein Multiplex quantification.
Below you’ll find a selection of publications published in 2015 based on various types of Antibody Arrays:
- Human Cytokine array 6 in Blood – Balakumaran A. et al. “Bone marrow skeletal stem/progenitor cell defects in patients with dyskeratosis congenita and telomere biology disorders. Blood. 2015 Jan 29;125(5):793-802. doi: 10.1182/blood-2014-06-566810.
- Human Cytokine array 5 in Oncogene – Sharif GM. et al. “Cell growth density modulates cancer cell vascular invasion via Hippo pathway activity and CXCR2 signaling.” Oncogene. 2015 Mar 16. doi: 10.1038/onc.2015.44.
- Mouse Cytokine array 1000 in PLoS One – Arshad A et al. (2015) “Simultaneous Irradiation of Fibroblasts and Carcinoma Cells Repress the Secretion of Soluble Factors Able to Stimulate Carcinoma Cell Migration.” PLoS ONE 10(1): e0115447. doi:10.1371/journal. pone.0115447.
- Mouse Inflammation 1 in Laboratory Investigations – Wen J. et al. “Low doses of CMV induce autoimmune-mediated and inflammatory responses in bile duct epithelia of regulatory T cell-depleted neonatal mice. Lab Invest. 2015 Feb;95(2):180-92. doi: 10.1038/labinvest.2014.148.
- Mouse Q4000 in Clinical and Vaccine Immunology – Kurtz S., Elkins K. “Correlates of vaccine-induced protection against TB immune revealed in comparative analyses of lymphocyte populations.” Clinical and Vaccine Immunology, Accepted manuscript posted online 12 August 2015, doi: 10.1128/CVI.00301-15.
- Human G1000 in PLoS One – Gomez DL et al. (2015) “Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity for Endocrine Cell Fate. PLoS ONE 10(8): e0133862. doi:10.1371/ journal.pone.0133862.
- Human Apoptosis Array in Drug Design and Development – Ahmadipour F. et al. “Koenimbin, a natural dietary compound of Murraya koenigii (L) Spreng: inhibition of MCF7 breast cancer cells and targeting of derived MCF7 breast cancer stem cells (CD44+/CD24-/low): an in vitro study.” Drug Des Devel Ther. 2015 Feb 24;9:1193-208. doi: 10.2147/DDDT.S72127.
Contact us to know more on how we can help you to publish in high-quality journals!
Tumours are composed by a heterogeneous group of cells from diverse organs, ranging from stem cells and endothelial cells, to a wide range of immune cells. The plethora of secretory signals from cancer cells have numerous effects that help promote tumour growth and progression, while also perturbing the immunologic surveillance of developing tumours.
Cancerous cells express their own profile of cytokines and chemokines that facilitate inflammation, cell growth, and recruitment of new blood vessels. It is also recruiting accessory cell populations for their survival and immunologic avoidance. Collectively, these local changes promote the developing tumour microenvironment (TME). As we have seen in previous posts, multiplexed immunoassays remain the best and most complete means to study the proteomic changes within the TME, as they afford the most global view of protein changes from numerous and disparate cell populations.
High-density protein expression profiling is now possible with the latest advancements in multiplex ELISA platforms. They enable the detection of a diversity of novel cytokine interactions in tumour cell populations. As these unique pathways are determined, more traditional biomolecular studies can then define these networks. Multiplex ELISAs and antibody arrays therefore represent powerful tools for the identification of new cancer biomarkers, either from the local TME, or from the cancer cells themselves.
This post is the first one of a series aiming at describing the mechanisms of TME and immunosurveillance and at introducing the reliable immunoassays to analyse cellular crosstalks at the protein level. Thanks to Jarad Wilson, from Raybiotech Inc., for his help on making this series!
Tumour immunosurveillance crosstalks – the main actors to monitor
Tumour immunosurveillance is the identification and elimination of cancer cells by the immune system. This process is predominantly mediated by CD8+ cytotoxic T lymphocytes (CTLs), natural killer cells (NK), neutrophils, and several subtypes of effector CD4+ T cells (CD4s), with accessory roles performed by antibody producing B cells and macrophages (Mφ) amongst others.
Effective immunosurveillance requires the innate immune system’s recognition of the tumour’s presence and the subsequent full activation and maturation of antigen presenting cell (APC) populations, namely the dendritic cell (DC) population. This maturation process increases APC surface expression of MHC-antigen complexes, increases APC endocytic sampling, upregulates cytokines that recruit T cell populations (IL-6, IL-12), and increases surface expression of T cell costimulatory ligands (CD80,CD86, ICOS).
Fully mature DC populations are potent anti-tumour APCs capable of activating all forms of tumour-specific T cell populations. Activated CD8 T cells differentiate to form CTLs which have profound inflammatory and cytolytic functions, while activated effector CD4 T cells secrete cytokines that have immunostimulatory and chemotactic effects.
Specifically, effector CD4 T cells develop into a T helper 1 (Th1) population which secretes IL-2 to promote CTL and further CD4 T expansion, TNF-α to inflame the site and recruit other immune cells, and IFN-γ which has anti-tumor and inflammatory functions. IFN-γ also functions to activate and drive Mφ populations into an M1 phenotype, which further produce IL-1α and IL-1β, feeding back to promote Th1 effector CD4+ polarisation and reinforcing the anti-tumour immune programming.
Collectively, these targeted immune responses are capable of shrinking the cancer population, but such a targeted measure can create selective pressures on those tumour cells capable of avoiding this surveillance program. The development of tumorigenesis requires the eventual subversion of immunosurveillance, a multi-step process leading to eventual escape from immunologic recognition and control.
Th1 lymphocytes and M1 Mφ are the primary sources of pro-inflammatory cytokines that promote cancer immunosurveillance and cytotoxicity. Their interactions are mutually reinforcing: Secretion IFN-γ by Th1 cells results in the recruitment and maintenance of M1, while IL-12 produced by M1 macrophages recruits, activates and maintains Th1 cells. Secretion of MIG/CXCL9 and IP-10/CXCL10 also promotes the recruitment of Th1 cells and CTLs and inhibits angiogenesis. IL-1α, IL-1β and IL-6 form an autocrine feedback loop by stimulation of myeloid differentiation primary response gene 88 (MyD88)-mediated activation of NF-κB signaling. TNF-α, also released by the activation of NF-κB signaling, which activates APC functions of DCs and the recruitment and cytotoxic activation of M1 macrophages, effector CD4+ T cells, and CD8+ cells, as well as the recruitment of NK cells.
Th2 lymphocytes, M2 macrophages and MDSCs mutually reinforce the proliferation and phenotypes of one another, as well as maintaining tumor-promoting inflammation and angiogenesis. These cells, along with T Regulatory lymphocytes (TREGs) suppress the activity and proliferation of tumor-suppressing cells, including Th1, M1 and cytotoxic T cells and NK cells.
It should be noted that M1 &M2 Mφ can interconvert, but these phenotypes are stable as the M1 and M2 expression profiles reinforce their own macrophage phenotypes, while suppressing the other. Similarly, Th1 & Th2 lymphocytes, as well as TREG & Th17 lymphocytes tend to self-reinforce their own activation profiles and inhibit the other.
Having a look at this picture, one would think that the immune system controls the growth and dissemination of cancer cells. We know that, unfortunately, this is not always true.
So…what happens when immunosurveillance fails and why does it fail? Stay tuned for our next post!
Looking for validated immunoassays to analyse tumour crosstalks? Please do not hesitate to leave a message below.