• Michael Misialek, MD

Targeting the Tumor Microenvironment in Cancer

For many years the tissues and cells surrounding a malignant tumor were thought to be passive bystanders playing little, if any, role in tumor development. Under the microscope one frequently observes fibrosis, angiogenesis and some degree of inflammatory infiltrate around tumors. Only recently have the specific components of this tumor microenvironment been elucidated. Instead of serving an innocent bystander role, each element in fact functions in a complex interconnected network of stimulatory and inhibitory actions crucial to tumor development and destruction.

Traditionally cancer has been treated using cytotoxic drugs, causing the death of cancer cells, but also resulting in the death of normal cells. This nonselective approach, still in use today, is the reason for many of the typical side effects of chemotherapy. By targeting unique tumor characteristics, a more effective destruction of tumor can be achieved, while sparing normal tissues. This approach, termed "precision medicine", is the hottest area in tumor research.

What is the tumor microenvironment?

The tumor microenvironment comprises all the cells and tissues surrounding a tumor. These cells are often recruited to tumors directly or as a result of tumor growth and are derived from either hematopoietic or mesenchymal origin. Each has a specific function in the body's suppressive efforts on tumor growth.

The tumor microenvironment can be leveraged to battle cancer. Knowing each of the cell's functions, therapeutic strategies have been developed to alter the tumor microenvironment in the hopes to suppress tumor growth.

How pathologists are crucial

Pathologists are crucial in identifying the tumor microenvironment. Using such techniques as multiplexed immunohistochemistry, immunofluorescence and mass spectrometry, multiple cell types and proteins can be analyzed simultaneously.

Combination approach

Using both traditional chemotherapy along with precision medicine approaches, tumors can be targeted from many angles. Some of the important pathways being investigated include the below areas:

  • RNA based gene signatures that reflect the tumor immune microenvironment

  • CD8 infiltrating T cells

  • PD-L1 expression

  • IFN gamma signature genes

  • Tumor mutational burden

The precision medicine revolution has fundamentally changed cancer care. With a deeper understanding of the mutations behind cancer, and ever increasingly easier and less costly tumor sequencing methods, cancer is becoming a manageable chronic disease rather than a death sentence of the past. The contributions of pathologists have been indispensible throughout this journey. They are a crucial member of the care team.

#precisionmedicine #microenvironment #stroma #immunotherapy

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