New research reveals that immune cells can independently navigate complex environments by actively shaping chemical cues, exhibiting a higher capacity for self-directed movement than previously appreciated, a finding that has profound implications for understanding immune responses and cancer metastasis.

Cell directional movement is an indispensable basic phenomenon in life. It is an important prerequisite for ontogeny, vascular reorganization, immune response, etc. InFLAMES researcher Jonna Alanko revealed that these cells are not just passive responders to chemical signals in their environment. Instead, they actively modify these signals and self-organize to navigate complex environments.

A study conducted by postdoctoral researcher Jonna Alanko focused on the movement and navigation of immune cells in the body. Chemokines are a class of signaling proteins that play a crucial role in guiding immune cells to specific locations. For example, chemokines are formed in lymph nodes and create chemical cues, known as chemokine gradients, in the body for cells to track. Alanco believes that these chemokine gradients are like odor trails left in the air, and the farther away from the odor source, the weaker the smell.

Conventional wisdom holds that immune cells recognize targets by tracking existing chemokine gradients. In other words, cells that follow these cues are seen as passive actors, which is not the case.

Dendritic cells navigate the microscopic maze with the help of chemokine gradients they create. The cell nuclei are blue in the upper image, and the lines in the lower image represent cell movement. Image source: Jonna Alanko, University of Turku

"We demonstrate for the first time that, contrary to previous concepts, immune cells do not require existing chemokine gradients to find their own direction. Even in complex environments, they can create their own gradients to migrate collectively and efficiently."

Immune cells have receptors that sense chemokine signals. One of these receptors is called CCR7, which is found on dendritic cells. Dendritic cells are professional antigen-presenting cells that play an important role in activating the entire immune response. They need to localize the infection, identify it, and then migrate the information to the lymph nodes. In lymph nodes, dendritic cells interact with other cells of the immune system to initiate an immune response against pathogens.

Research conducted by Alanko found that dendritic cells not only receive chemokine signals through their CCR7 receptors, but also actively shape their chemical environment by consuming chemokines. By doing so, dendritic cells form local gradients that guide the movement of themselves and other immune cells. The researchers also found that T cells, another type of immune cell, also benefit from these self-generated gradients to enhance their own directional movement.

"When immune cells are able to generate chemokine gradients, they can avoid upcoming obstacles in a complex environment and guide themselves and other immune cells to move in a directional manner," explains Joana Alainco.

This discovery deepens our understanding of how immune responses are coordinated in the body. However, it also reveals how cancer cells direct their movement to create metastasis.

"The CCR7 receptor is also found in many cancer types, and in these cases it is thought to promote cancer metastasis. Cancer cells may even use the same mechanisms as immune cells to guide their movement. Therefore, our findings may help to design new strategies to alter immune responses as well as target certain cancers."

Reference Jonna Alanko, Mehmet Can Uçar, Nikola Canigova, Julian Stopp, Jan Schwarz, Jack Merrin, Edouard Hannezo, and Michael Sixt published in Science Immunology on September 1, 2023: "CCR7 acts simultaneously as a sensor and sink for CCL19 to coordinate the collective migration of leukocytes."

DOI:10.1126/sciimmunol.adc9584

Compiled source: ScitechDaily