Infographic: How Immunotherapy Could Boost Stem-Like T Cells
Infographic: How Immunotherapy Could Boost Stem-Like T Cells

Infographic: How Immunotherapy Could Boost Stem-Like T Cells

Cancer therapies could potentially be more effective if their development took into account the cells that give rise to tumor-fighting cells.

Daniel E. Speiser and Werner Held
Jul 13, 2020

ABOVE: © LUCY READING-IKKANDA

The body’s defense system against infection also fights tumors, generating tumor resident stem-like T cells and killer T cells that express inhibitory receptors such as PD-1. When PD-1 binds to PD-L1 or PD-L2 on tumor cells or other cells, T cell functions are subdued. Checkpoint blockade treatments interrupt this interaction. This allows stem–like T cells to proliferate and to produce new killer T cells that can now kill tumor cells.

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Part of the body’s natural defense system against cancer involves dendritic cells taking up tumor-derived proteins and presenting them to antigen naive CD8+ T cells present in lymph nodes. The stimulated T cells can then migrate to the tumor.

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In the tumor, chronic activation yields stem–like T cells and killer T cells that express inhibitory receptors such as PD-1. The binding of PD-1 to PD-L1 or PD-L2 ligands on tumor cells deactivates killer T cells and prevents the killing of cancer cells.

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Treatment with checkpoint blockade immunotherapies, such as antibodies to PD-1, can prevent the interaction of PD-1 with PD-L1/2. This enables stem-like T cells to proliferate and produce more killer T cells that can now kill cancer cells.

Adoptive Cell Therapy and STEM CELL–LIKE T Cells

In patients with metastatic disease, tumor tissue can be surgically removed and immune cells extracted from it. The T cells, which include both cells that can fight the tumor and cells that cannot, are cultured with specific growth factors to increase their numbers and restore the functionality of cells that have become exhausted and thus less effective. This T cell mixture is then reinfused into the patient, with the aim of increasing the number of functional cells that can kill tumor cells and that will persist in the patient. The number of stem-like CD8+ T cells—which sustain the production of killer CD8+ T cells—that make it back into the patient is currently unclear. But the importance of these cells to sustain tumor-fighting in response to checkpoint blockade raises the possibility that the conditions used to expand cells for infusion can be further optimized to favor higher proportions of stem-like CD8+ T cells.

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In patients with metastatic disease, immune cells  (T cells) can be extracted from tumor tissue.

fighting in response to checkpoint blockade in two ways: they can differentiate into killer T cells that can kill cancer cells and also proliferate into more stem cells. This raises the possibility that the conditions used to expand cells for infusion should be further optimized to favor higher proportions of stem-like T cells.

The T cells, which include both cells that can fight the tumor (killer T cells) and cells that cannot, are cultured with specific growth factors to increase their numbers. 

The cultured T cells are infused into the patient with the aim of increasing the number of tumor-fighting T cells that the patient can produce.

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