Cell competition is a pervasive phenomenon in living organisms that has important implications for the maintenance of tissue homeostasis, biological development, and disease progression. Studying the survival competition that macrophages engage in with cancer cells has the potential to reveal new pathways of tumor suppression.

Fig.1 The nutritional competition between tumor cells and immune cells inside tumors.¹

Here, Creative Biolabs shares some information about the important regulatory role of macrophages in competition with cancer cells, providing new insights into immunotherapy.

The Intense Battle: Macrophages VS Cancer Cells

• When cancer cells emerge in the body, they are immediately confronted by a sentinel of macrophages. Macrophages utilize a series of pattern recognition receptors (PRRs) to recognize molecules associated with cancer cells, such as damage-associated molecular patterns (DAMP) and pathogen-associated molecular patterns (PAMP).
• Along with that, cancer cells adopt various strategies to evade macrophages. One such strategy is to hijack inflammatory signals and share immune checkpoints.
• This competition continues to be profoundly influenced by the recruitment and polarization of tumor-associated macrophages (TAMs). Pro-inflammatory TAMs contribute to the elimination of cancer cells, whereas immunosuppressive TAMs promote tumor progression.
• Macrophages and cancer cells possess their own antagonistic effects.
  
  • Macrophages strengthen the battle line by phagocytosis, release cytotoxic molecules, secrete cytokines and chemokines, and coordinate the recruitment of other immune cells.
  • Cancer cells employ a variety of countermeasures against macrophage-mediated destruction. They secrete a variety of chemokines and growth factors that attract immunosuppressive cells and also manipulate their surroundings.

Competition for Nutrients Between Tumor Cells and Macrophages

Normal proliferation and differentiation of macrophages cannot be achieved without nutrient metabolism. In contrast, the metabolic patterns and immune functions of TAMs change in response to changes in the tumor microenvironment. Changes in these metabolic pathways also directly affect TAM immune function and thus tumor progression.

• Changes in glucose metabolism affect the rapid consumption and energy requirements of macrophage metabolic intermediates, thereby altering the M1/M2 polarization of macrophages and regulating their immune function.
• Altered lipid metabolism severely affects macrophage function and cancer progression. Reprogramming of lipid metabolism affects tumor proliferation, metastasis, and invasion, and also significantly influences TAM function and phenotypic differentiation.
• Macrophage maturation, differentiation and function are highly dependent on amino acid transport and metabolism. Amino acids derived from the tumor microenvironment are used to support tumor cell proliferation, invasion and immune escape.

Unveiling the Therapeutic Potential

As our understanding of how macrophages compete with cancer cells continues to grow, new therapeutic avenues are emerging around regulating macrophage activity.

• Immunotherapy Targeting Macrophages
• Reprogramming TAM

The battle between macrophages and cancer cells continues. With each revelation, we learn more about the complex interactions, molecular dialogues and intricate balances that determine the outcome of this conflict. Researchers are eagerly exploring ways to tip the scales in favor of cancer-fighting immunity.

Creative Biolabs harnesses the power of macrophages as well as studying the complex crosstalk between these cells and cancer cells. For more specific research services, contact us for more details.

Reference

1. Xia, Longzheng, et al. "The cancer metabolic reprogramming and immune response." Molecular cancer 20 (2021): 1-21.