Peripheral T cell expansion predicts tumour infiltration and clinical response.

Abstract

Despite the resounding clinical success in cancer treatment of antibodies that block the interaction of PD1 with its ligand PDL11, the mechanisms involved remain unknown. A major limitation to understanding the origin and fate of T cells in tumour immunity is the lack of quantitative information on the distribution of individual clonotypes of T cells in patients with cancer. Here, by performing deep single-cell sequencing of RNA and T cell receptors in patients with different types of cancer, we survey the profiles of various populations of T cells and T cell receptors in tumours, normal adjacent tissue, and peripheral blood. We find clear evidence of clonotypic expansion of effector-like T cells not only within the tumour but also in normal adjacent tissue. Patients with gene signatures of such clonotypic expansion respond best to anti-PDL1 therapy. Notably, expanded clonotypes found in the tumour and normal adjacent tissue can also typically be detected in peripheral blood, which suggests a convenient approach to patient identification. Analyses of our data together with several external datasets suggest that intratumoural T cells, especially in responsive patients, are replenished with fresh, non-exhausted replacement cells from sites outside the tumour, suggesting continued activity of the cancer immunity cycle in these patients, the acceleration of which may be associated with clinical response.

• Authors: Thomas D Wu, Shravan Madireddi, Patricia E de Almeida, Romain Banchereau, Ying-Jiun J Chen, Avantika S Chitre, Eugene Y Chiang, Hina Iftikhar, William E O'Gorman, Amelia Au-Yeung, Chikara Takahashi, Leonard D Goldstein, Chungkee Poon, Shilpa Keerthivasan, Denise E de Almeida Nagata, Xiangnan Du, Hyang-Mi Lee, Karl L Banta, Sanjeev Mariathasan, Meghna Das Thakur, Mahrukh A Huseni, Marcus Ballinger, Ivette Estay, Patrick Caplazi, Zora Modrusan, Lélia Delamarre, Ira Mellman, Richard Bourgon, Jane L Grogan
• Journal: Nature (Nature) Vol. 579 Issue 7798 Pg. 274-278 (03 2020) ISSN: 1476-4687 [Electronic] England
• PMID: 32103181 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Receptors, Antigen, T-Cell
• atezolizumab

Topics

• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Clone Cells
• Humans
• Lymphocytes, Tumor-Infiltrating (cytology, metabolism)
• Neoplasms (drug therapy, immunology, pathology)
• Pharmacogenomic Variants
• Receptors, Antigen, T-Cell (genetics)
• T-Lymphocytes (cytology, metabolism)
• Transcriptome