An intra-tumoral niche maintains and differentiates stem-like CD8 T cells

• Published in: Nature (London) Vol. 576; no. 7787; pp. 465 - 470
• Main Authors: Jansen, Caroline S, Prokhnevska, Nataliya, Master, Viraj A, Sanda, Martin G, Carlisle, Jennifer W, Bilen, Mehmet Asim, Cardenas, Maria, Wilkinson, Scott, Lake, Ross, Sowalsky, Adam G, Valanparambil, Rajesh M, Hudson, William H, McGuire, Donald, Melnick, Kevin, Khan, Amir I, Kim, Kyu, Chang, Yun Min, Kim, Alice, Filson, Christopher P, Alemozaffar, Mehrdad, Osunkoya, Adeboye O, Mullane, Patrick, Ellis, Carla, Akondy, Rama, Im, Se Jin, Kamphorst, Alice O, Reyes, Adriana, Liu, Yuan, Kissick, Haydn
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.12.2019
• Subjects: Animals; Antigen Presentation - genetics; Antigen Presentation - immunology; Antigen-presenting cells; Antigens; Cancer; CD8 antigen; CD8 lymphocytes; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation; Cell proliferation; Development and progression; Disease Progression; DNA methylation; Effector cells; Epigenesis, Genetic; Epigenetics; Health aspects; Hepatocyte Nuclear Factor 1-alpha - metabolism; Human behavior; Humans; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - cytology; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Metastases; Mice; Neoplasms - immunology; Neoplasms - pathology; Oncology, Experimental; Patients; Physiological aspects; Population; Stem Cell Niche - immunology; Stem Cells - cytology; T cell receptors; Transcription factors; Transcription, Genetic; Tumor Escape - genetics; Tumor Escape - immunology; Tumors; Viral infections; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-019-1836-5

Tumour-infiltrating lymphocytes are associated with a survival benefit in several tumour types and with the response to immunotherapy . However, the reason some tumours have high CD8 T cell infiltration while others do not remains unclear. Here we investigate the requirements for maintaining a CD8 T cell response against human cancer. We find that CD8 T cells within tumours consist of distinct populations of terminally differentiated and stem-like cells. On proliferation, stem-like CD8 T cells give rise to more terminally differentiated, effector-molecule-expressing daughter cells. For many T cells to infiltrate the tumour, it is critical that this effector differentiation process occur. In addition, we show that these stem-like T cells reside in dense antigen-presenting-cell niches within the tumour, and that tumours that fail to form these structures are not extensively infiltrated by T cells. Patients with progressive disease lack these immune niches, suggesting that niche breakdown may be a key mechanism of immune escape.