Optimizing Cancer Immunotherapy Through Memory T Cell Collaboration

Both circulating and tissue-resident memory T cells are needed to create an optimal immune response to cancer, according to a study published in Nature Communications.

Immunotherapy is boasted as a major scientific advancement, and uses the body’s own immune system to target and kill cancer cells; however, the treatment does not work for everyone.

“Cancer escapes the control of the immune system because the cytotoxic T lymphocytes that could recognize and eliminate tumor cells are inhibited,” said lead author David Sancho. “Current immunotherapy is based the reactivation of these T lymphocytes; however, little is known about how they can be generated more effectively, and in particular how immune memory can be triggered to prevent the development of tumors and metastasis.”

For the study, investigators sought to generate cytotoxic memory T cells that specifically target cancer using different methods of vaccination with tumor antigens.

The findings showed that depending on the vaccination method, memory T lymphocytes obtained circulate between the blood and tissues or resided in the tissues and do not circulate.

Although tissue-resident memory T cells have shown more efficacy at fighting viral reinfections, their role in anti-tumor immunity remained unknown until now.

The investigators compared the efficiency of anti-tumor immunity conferred by each memory T cell type.

“We found that the circulating and tissue-resident memory cells cooperate to generate the optimal response,” first author Michel Enamorado said. “Tissue-resident memory cells generate an alert state that attracts and reactivates the circulating memory cells, resulting in a faster and more effective immune response.”

Additionally, the treatment efficacy further improved when the adoptive transfer of tumor-targeting T cells was combined with the current clinical strategy of reactivating the T cell antitumor response with antibodies to the PD-1 receptor.

Transferred circulating memory T cells can convert themselves into resident memory cells in the presence of infection and cancer, according to the authors. Reactivation of the anti-tumor response in cytotoxic memory T cells needs the DC1 subtype of dendritic cells.

The findings suggest that generating an optimal anti-tumor immune response requires the collaboration of circulating and tissue-resident memory T cells, both of which can be reactivated via current immunotherapy treatments.