The Role of Tumor Microenvironments in Cancer Development & Treatment

Fanyun Fang

Fanyun Fang
Dec 3, 2021 1:00:00 PM

The tumor is an abnormal tissue mass formed when cells divide and grow excessively within the body. Tumors can be benign (not cancerous) or malignant (cancerous). Benign tumors may become larger but do not spread to nearby tissue or other parts of the body. Malignant tumors, on the other hand, can spread nearby to tissue and can also be transmitted to other parts of the body through the blood and or lymphatic system.1 But we are no strangers to tumors and how the develop.

On the other hand, many of us aren’t as familiar with a tumor’s environment. Tumor progression is profoundly affected by the subtle interaction of tumor cells with immune and non-immune cells within their environment. In particular, the interactions with the immune cell component of a tumor are fundamental in determining whether primary tumors are eradicated, metastasized, or established by dormant micro metastases.3 The environment that a tumor grows in is also much more complex than one would think because of its highly variable cell composition, large number of proteins, and structures involved in tumor formation.


This being said, tumor microenvironment includes:
• Heterogeneous populations of cancer cells
• A variety of resident and osmotic host cells
• Secretion factors
• Extracellular matrix proteins

 

T Cell

Figure 1 source: National Cancer Institute. (2020, January 15). What is the tumor microenvironment? Image details. NCI Visuals Online. Retrieved from https://visualsonline.cancer.gov/details.cfm?imageid=12496.

Key Role in Cancer Development

The extracellular matrix (ECM) is a major structural component of the tumor microenvironment.5 While a tumor microenvironment provides all the nutrients (oxygen, glucose, etc.) needed for a tumor to grow, the ECM contains all the cytokines, growth factors, and hormones secreted by stromal and tumor cells. As time goes on, and the immune and non-immune cells of the tumor microenvironment interact with each other and can allow the cancer to grow. Then, the immune microenvironment helps cancer cells select dominant cells, allowing tumors to progress and or grow. The ECM can aid tumor development in the following ways:

  1. Affect tumors through extracellular secretion.
  2. Change the phenotypic type of somatic cell or tumor cells.
  3. Help tumors get rid of immune monitoring.
  4. Provide a low-oxygen or acidic environment in which tumor cells have a more significant survival advantage than normal cells.

 

Methods of Tumor microenvironment Phenotyping

The tumor immune microenvironment phenotyping (TME) method utilizes multiplex immunohistochemistry (mIHC) and immunofluorescence (IF) to explore specific immune cells. IF is a common laboratory technique used to determine the location of an antigen in tissues by its reaction with an antibody labeled with a fluorescent dye. With this fluorescent dye attached, the target molecule can be depicted in a way that allows researchers to study the distribution within the sample. Furthermore, mIHC is a form of immunostaining that uses enzymes or fluorescent-related antibodies to identify antigens in tissue parts. This technique can be used to track multiple markings simultaneously without the need for laborious dye cycling procedures.4 Overall, it has been found that the TME phenotyping methods discussed previously can contribute to cancer patients' clinical prognosis and efficacy prediction.

Improving Cancer Treatment

It is important to understand TME and the different immune cells in it to leverage the immunotherapy and the developing new treatments, as many cancer types often have similar tumor microenvironments. Scientists can use different predefined cell type markers to describe the state and spatial arrangement of tumor cells and different types of osmosis strobe cells, analyze TME to discover new cell phenotypes and disease mechanisms, develop targeted therapies, study drug efficacy, and predict the prognosis for cancer treatment.

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Current Developments

In recent years, many studies have shown that significant epigenetic changes lead to abnormal gene expression in tumor microenvironment cells. The characteristics of the gene expression from tumor stroma can predict clinical outcomes. Given these recent findings, researchers are increasingly interested in the cancer microenvironment as a prognostic factor and potential therapeutic target. New therapies targeting matrix components are being developed.

Monoclonal antibody (mAb) therapy has only recently become one of the main ways to treat cancer.6 Monoclonal antibodies target tumor cell-specific or over-expressed antigens that can cause tumor cell death. When a mAb binds to its target growth factor receptor and manipulates its activation state or blocks ligand binding, the signals that promote tumor growth and survival will be disturbed.

According to statistics, many monoclonal antibodies have been approved for oncology, autoimmune diseases, chronic diseases, and more diseases. More than 80 antibody therapies have received regulatory approvals in Europe and the United States.7 In 2017 alone, global sales of therapeutic antibodies exceeded $100 billion US dollar.8

How ABclonal can Help

Scientists can effectively and accurately characterize the tumor microenvironment using antibodies through IF and mIHC to understand how different cell types in the tumor microenvironment interact and communicate with each other through signaling networks. Once researchers understand these signaling networks, they will be able to develop different ways to block these signals, thereby preventing tumors from growing. They can also utilize mAb therapies to target tumors. At ABclonal Technology, we offer multiple antibodies for tumor-microenvironment phenotyping.

 

Featured Antibodies from ABclonal for Tumor microenvironment Phenotyping

 

Category

Target

Cat. No.

Product Name

Applications

Reactivity

Cancer cell related

E-Cadherin

A3149

E-Cadherin mouse mAb

WB,IHC,FC

Human,Mouse

EpCAM

A19301

EpCAM Rabbit mAb

WB,IHC,IF

Human,Mouse,Rat

Cytokeratin 8

A1204

[KO Validated] Cytokeratin 8 Rabbit pAb

WB, IHC, IF

Human, Mouse

Cytokeratin 14

A19039

Cytokeratin 14 (KRT14) Rabbit mAb

WB, IHC

Human, Mouse, Rat

Cytokeratin 18

A19778

Cytokeratin 18 (KRT18) Rabbit mAb

WB, IHC, IF

Human, Mouse, Rat

Cytokeratin 19

A19040

Cytokeratin 19 (KRT19) Rabbit mAb

WB, IHC

Human, Mouse, Rat

Claudin 1

A2196

Claudin 1 Rabbit pAb

WB, IHC

Human, Mouse, Rat

CEACAM1

A11626

CEACAM1 Rabbit mAb

WB,IHC

Human,Rat

CEACAM5

A18131

CEACAM5 Mouse mAb

WB,IHC

Human

MUC1

A19081

MUC1 Rabbit mAb

WB, IHC

Human, Mouse, Rat

CD13/ANPEP

A11669

CD13/ANPEP Rabbit mAb

WB, IHC, IF

Human, Mouse, Rat

CD34

A19015

CD34 Rabbit mAb

WB, IHC

Human, Mouse, Rat

CD38

A20215

CD38 Rabbit mAb

IF, FC

Human

CD82

A9264

CD82 Rabbit mAb

WB, IHC, IF

Human, Mouse

CD83

A4234

CD83 Rabbit mAb

WB, IF

Human, Mouse

CD90/Thy1

A12623

CD90/Thy1 Rabbit mAb

WB,IHC

Human,Rat

CD105/Endoglin

A19008

CD105/Endoglin Rabbit mAb

WB, IHC

Human

CD117/c-Kit

A0357

CD117/c-Kit Rabbit pAb

WB, IHC, IF

Human, Mouse, Rat

CD138/Syndecan-1

A4174

CD138/Syndecan-1 Rabbit mAb

WB, IHC, IF

Human, Mouse, Rat

AFP

A11865

Alpha-Fetoprotein (AFP) Mouse mAb

WB, IHC, IF

Human, Mouse, Rat

ALDH1A1

A0157

ALDH1A1 Rabbit mAb

WB,IF

Human, Mouse, Rat

CD44

A19020

[KO Validated] CD44 Rabbit mAb

WB,IHC

Human

CD133

A12711

[KO Validated] CD133 Rabbit pAb

WB,IF,IP

Human,Mouse,Rat

SOX2

A19118

[KO Validated] SOX2 Rabbit mAb

WB

Human,Mouse,Rat

Fibroblasts related

α-SMA

A17910

α-Smooth Muscle Actin (ACTA2) Rabbit mAb

WB,IHC,IF

Human,Mouse,Rat

FSP1/S100A4

A19109

FSP1/S100A4 Rabbit mAb

WB,IHC,IF

Human,Mouse,Rat

Fibronectin

A16678

Fibronectin Rabbit pAb

WB, IHC, IF

Human, Mouse

Vimentin

A19607

[KO Validated] Vimentin Rabbit mAb

WB, IHC, IF, IP

Human, Mouse, Rat

FGFR3

A19052

FGFR3 Rabbit mAb

WB, IHC, IF

Human, Mouse, Rat

FGFR4

A9197

FGFR4 Rabbit mAb

WB, IHC

Human, Mouse

PDGFRB

A19531

PDGF Receptor beta Rabbit mAb

WB, IF

Human, Mouse, Rat

T cell related

CD3D

A9700

CD3D Rabbit mAb

WB, IF

Human, Mouse, Rat

CD3E

A19017

CD3 epsilon Rabbit mAb

WB, IHC

Human

CD3E/G

A20213

CD3(epsilon+gamma)/CD3E+CD3G Rabbit mAb

WB, IF, FC, ELISA

Human

CD4

A19018

CD4 Rabbit mAb

WB, IHC

Human

CD8

A0663

CD8A Rabbit mAb

WB, IHC

Human

B cell related

CD19

A19013

CD19 Rabbit mAb

WB, IHC

Human

CD20

A4893

CD20 Rabbit mAb

WB, IHC, IF

Human

CD79a

A19024

CD79a Rabbit mAb

WB, IHC

Human

CD79b

A4362

CD79B Rabbit mAb

WB, IHC, IF

Human, Mouse, Rat

NK cell marker

NCAM1/CD56

A7913

NCAM1 / CD56 Rabbit pAb

WB, IHC, IF

Human, Mouse, Rat

Cytotoxic molecules

Granzyme B

A2557

Granzyme B Rabbit pAb

WB, IHC, IF

Human, Mouse, Rat

Perforin

A0093

Perforin Rabbit pAb

WB, IHC, IF

Human, Mouse, Rat

Endothelial cell marker

CD31

A18643

CD31/PECAM1 Rabbit mAb

WB, IHC

Human

CD31

A4900

CD31/PECAM1 Rabbit mAb

WB, IF

Human, Mouse

CD31

A19014

CD31/PECAM1 Rabbit mAb

WB, IHC

Human

Immune checkpoints

CD27

A11505

CD27 Rabbit mAb

WB,IF

Human,Rat

CD28

A20346

CD28 Rabbit mAb

FC, ELISA

Human

CD40

A20214

CD40 Rabbit mAb

WB, IF, FC, ELISA

Human

Arginase 1

A4923

Arginase 1 (ARG1) Rabbit mAb

WB, IHC, IF

Human, Mouse, Rat

CD112

A9622

Nectin 2/CD112 Rabbit mAb

WB, IHC

Human, Mouse, Rat

CD274/PD-L1

A19135

[KO Validated] PD-L1 Rabbit mAb

WB, IHC

Human, Rat

CD274/PD-L1

A20344

PD-L1 Rabbit mAb

WB, IHC

Human

CD274/PD-L1

A20270

PD-L1 Rabbit mAb

WB, FC, ELISA

Human

 

References:

Ham, S., Lima, L. G., Lek, E., & Möller, A. (2020, June 23). The impact of the cancer microenvironment on macrophage phenotypes. Frontiers. Retrieved from https://www.frontiersin.org/articles/10.3389/fimmu.2020.01308/full.

 Jin, MZ., Jin, WL. The updated landscape of tumor microenvironment and drug repurposing. Sig Transduct Target Ther 5, 166 (2020). https://doi.org/10.1038/s41392-020-00280-x

 Barry, S., Carlsen, E., Marques, P. et al. Tumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors. Oncogene 38, 5381–5395 (2019). https://doi.org/10.1038/s41388-019-0779-5

 Kevin Mayer. (2021, April 9). Immune cell profiles reveal cancer's leading indicators. Immune Cell Profiles Reveal Cancer’s Leading Indicators. Retrieved from https://www.genengnews.com/topics/cancer/immune-cell-profiles-reveal-cancers-leading-indicators/.

 Wang, M., Zhao, J., Zhang, L., Wei, F., Lian, Y., Wu, Y., Gong, Z., Zhang, S., Zhou, J., Cao, K., Li, X., Xiong, W., Li, G., Zeng, Z., & Guo, C. (2017). Role of tumor microenvironment in tumorigenesis. Journal of Cancer, 8(5), 761–773. https://doi.org/10.7150/jca.17648

 Cruz, E., & Kayser, V. (2019). Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy. Biologics : targets & therapy, 13, 33–51. https://doi.org/10.2147/BTT.S166310

 Zahavi, D., & Weiner, L. (2020). Monoclonal Antibodies in Cancer Therapy. Antibodies, 9(3), 34. https://doi.org/10.3390/antib9030034

Walsh, G. Biopharmaceutical benchmarks 2018. Nat Biotechnol 36, 1136–1145 (2018). https://doi.org/10.1038/nbt.4305

Tags: Antibodies, Cancer, Tumor, Antibody, Monoclonal Antibodies, IHC, IF

Fanyun Fang

Fanyun Fang

Fanyun Fang is student at Kent State University, majoring in pre-med Biology.