Dissecting tissue resident lymphocyte homeostasis in human cancer

Natural killer (NK) cells play a crucial role as early immune effectors in the defense against cancer, existing both in peripheral blood and as tissue-resident (TR) cells in human peripheral organs.

In our ongoing ERC Starting Grant project (Björkström, 2021-2025), we have meticulously mapped NK cell tissue-residency across various human tissues, unraveling the functional regulation of tissue-residency.

Leveraging these groundbreaking insights, we aim to address the next generation of immunological questions using state-of-the-art single-cell technologies and rare clinical samples.

Our hypothesis posits that the function and energy utilization of TR NK cells are intricately regulated across organs and within specific microniches, further modulated within the tumor microenvironment (TME).

We plan to conduct a spatial and metabolic assessment of TR NK cells in human tissues at steady state, followed by a detailed examination of the transcriptional, epigenetic, and metabolic footprint of tumor-infiltrating TR NK cells in primary liver cancer at the single-cell level. Additionally, we aim to spatially resolve their presence in the TME.

Finally, by utilizing a unique monozygotic twin cohort concordant for the same type of tumor, we will dissect the genetic (host and tumor) and environmental factors influencing cytotoxic lymphocyte organization within the TME. These insights are anticipated to form a foundational guide for refining cancer treatment strategies.