Intratumoral CD103+ CD8+ T Cells Predict Response to PD-L1 Blockade

Overview

Journal J Immunother Cancer

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2021 Apr 8

PMID 33827905

Citations 68

Authors

Romain Banchereau

Avantika S Chitre

Alexis Scherl

Thomas D Wu

Namrata S Patil

Patricia De Almeida

Edward E Kadel Iii

Shravan Madireddi

Amelia Au-Yeung

Chikara Takahashi

Ying-Jiun Chen

Zora Modrusan

Jacqueline McBride

Rhea Nersesian

Ehab A El-Gabry

Mark D Robida

Jeffrey C Hung

Marcin Kowanetz

Wei Zou

Mark McCleland

Patrick Caplazi

Shadi Toghi Eshgi

Hartmut Koeppen

Priti S Hegde

Ira Mellman

W Rodney Mathews

Thomas Powles

Sanjeev Mariathasan

Jane Grogan

William E OGorman

Affiliations

Soon will be listed here.

Abstract

Background: CD8+ tissue-resident memory T (T) cells, marked by CD103 () expression, are thought to actively suppress cancer progression, leading to the hypothesis that their presence in tumors may predict response to immunotherapy.

Methods: Here, we test this by combining high-dimensional single-cell modalities with bulk tumor transcriptomics from 1868 patients enrolled in lung and bladder cancer clinical trials of atezolizumab (anti-programmed cell death ligand 1 (PD-L1)).

Results: was identified as the most significantly upregulated gene in inflamed tumors. Tumor CD103+ CD8+ T cells exhibited a complex phenotype defined by the expression of checkpoint regulators, cytotoxic proteins, and increased clonal expansion.

Conclusions: Our analyses indeed demonstrate that the presence of CD103+ CD8+ T cells, quantified by tracking intratumoral CD103 expression, can predict treatment outcome, suggesting that patients who respond to PD-1/PD-L1 blockade are those who exhibit an ongoing antitumor T-cell response.

Citing Articles

Tissue-resident memory T cells in urinary tract diseases.

Xu G, Li Y, Lu G, Xie D Front Immunol. 2025; 16:1535930.

PMID: 40066439 PMC: 11891219. DOI: 10.3389/fimmu.2025.1535930.

Society for Immunotherapy of Cancer (SITC) consensus statement on essential biomarkers for immunotherapy clinical protocols.

Cottrell T, Lotze M, Ali A, Bifulco C, Capitini C, Chow L J Immunother Cancer. 2025; 13(3).

PMID: 40054999 PMC: 11891540. DOI: 10.1136/jitc-2024-010928.

The XCL1-XCR1 axis supports intestinal tissue residency and antitumor immunity.

Ferry A, Mempel K, Monell A, Reina-Campos M, Scharping N, Heeg M J Exp Med. 2025; 222(2.

PMID: 39841133 PMC: 11753173. DOI: 10.1084/jem.20240776.

Tertiary Lymphoid Structures are Linked to Enhanced Antitumor Immunity and Better Prognosis in Muscle-Invasive Bladder Cancer.

Lin J, Jiang S, Chen B, Du Y, Qin C, Song Y Adv Sci (Weinh). 2024; 12(7):e2410998.

PMID: 39739621 PMC: 11831474. DOI: 10.1002/advs.202410998.

Differential predictive value of resident memory CD8T cell subpopulations in patients with non-small-cell lung cancer treated by immunotherapy.

Paolini L, Tran T, Corgnac S, Villemin J, Wislez M, Arrondeau J J Immunother Cancer. 2024; 12(12.

PMID: 39631852 PMC: 11624836. DOI: 10.1136/jitc-2024-009440.

References

Mackay L, Minnich M, Kragten N, Liao Y, Nota B, Seillet C . Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science. 2016; 352(6284):459-63. DOI: 10.1126/science.aad2035. View

Farber D, Yudanin N, Restifo N . Human memory T cells: generation, compartmentalization and homeostasis. Nat Rev Immunol. 2013; 14(1):24-35. PMC: 4032067. DOI: 10.1038/nri3567. View

Ribas A . Adaptive Immune Resistance: How Cancer Protects from Immune Attack. Cancer Discov. 2015; 5(9):915-9. PMC: 4560619. DOI: 10.1158/2159-8290.CD-15-0563. View

Milner J, Goldrath A . Transcriptional programming of tissue-resident memory CD8 T cells. Curr Opin Immunol. 2018; 51:162-169. PMC: 5943164. DOI: 10.1016/j.coi.2018.03.017. View

Kim H, Song G, Park S, Jung M, Kim M, Kang H . Association Between Expression Level of PD1 by Tumor-Infiltrating CD8 T Cells and Features of Hepatocellular Carcinoma. Gastroenterology. 2018; 155(6):1936-1950.e17. DOI: 10.1053/j.gastro.2018.08.030. View

Mariathasan S, Turley S, Nickles D, Castiglioni A, Yuen K, Wang Y . TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018; 554(7693):544-548. PMC: 6028240. DOI: 10.1038/nature25501. View

Ganesan A, Clarke J, Wood O, Garrido-Martin E, Chee S, Mellows T . Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer. Nat Immunol. 2017; 18(8):940-950. PMC: 6036910. DOI: 10.1038/ni.3775. View

Simoni Y, Becht E, Fehlings M, Loh C, Koo S, Teng K . Bystander CD8 T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature. 2018; 557(7706):575-579. DOI: 10.1038/s41586-018-0130-2. View

Amsen D, van Gisbergen K, Hombrink P, van Lier R . Tissue-resident memory T cells at the center of immunity to solid tumors. Nat Immunol. 2018; 19(6):538-546. DOI: 10.1038/s41590-018-0114-2. View

10.

Scott A, Dundar F, Zumbo P, Chandran S, Klebanoff C, Shakiba M . TOX is a critical regulator of tumour-specific T cell differentiation. Nature. 2019; 571(7764):270-274. PMC: 7698992. DOI: 10.1038/s41586-019-1324-y. View

11.

Aran D, Looney A, Liu L, Wu E, Fong V, Hsu A . Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat Immunol. 2019; 20(2):163-172. PMC: 6340744. DOI: 10.1038/s41590-018-0276-y. View

12.

Xiong H, Mittman S, Rodriguez R, Pacheco-Sanchez P, Moskalenko M, Yang Y . Coexpression of Inhibitory Receptors Enriches for Activated and Functional CD8 T Cells in Murine Syngeneic Tumor Models. Cancer Immunol Res. 2019; 7(6):963-976. DOI: 10.1158/2326-6066.CIR-18-0750. View

13.

Hadley G, Higgins J . Integrin αEβ7: molecular features and functional significance in the immune system. Adv Exp Med Biol. 2014; 819:97-110. DOI: 10.1007/978-94-017-9153-3_7. View

14.

Lawrence M, Huber W, Pages H, Aboyoun P, Carlson M, Gentleman R . Software for computing and annotating genomic ranges. PLoS Comput Biol. 2013; 9(8):e1003118. PMC: 3738458. DOI: 10.1371/journal.pcbi.1003118. View

15.

Hegde P, Karanikas V, Evers S . The Where, the When, and the How of Immune Monitoring for Cancer Immunotherapies in the Era of Checkpoint Inhibition. Clin Cancer Res. 2016; 22(8):1865-74. DOI: 10.1158/1078-0432.CCR-15-1507. View

16.

Smazynski J, Webb J . Resident Memory-Like Tumor-Infiltrating Lymphocytes (TIL): Latest Players in the Immuno-Oncology Repertoire. Front Immunol. 2018; 9:1741. PMC: 6070600. DOI: 10.3389/fimmu.2018.01741. View

17.

Zhang N, Bevan M . Transforming growth factor-β signaling controls the formation and maintenance of gut-resident memory T cells by regulating migration and retention. Immunity. 2013; 39(4):687-96. PMC: 3805703. DOI: 10.1016/j.immuni.2013.08.019. View

18.

Sade-Feldman M, Yizhak K, Bjorgaard S, Ray J, de Boer C, Jenkins R . Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma. Cell. 2018; 175(4):998-1013.e20. PMC: 6641984. DOI: 10.1016/j.cell.2018.10.038. View

19.

Yost K, Satpathy A, Wells D, Qi Y, Wang C, Kageyama R . Clonal replacement of tumor-specific T cells following PD-1 blockade. Nat Med. 2019; 25(8):1251-1259. PMC: 6689255. DOI: 10.1038/s41591-019-0522-3. View

20.

Rosenberg J, Hoffman-Censits J, Powles T, van der Heijden M, Balar A, Necchi A . Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016; 387(10031):1909-20. PMC: 5480242. DOI: 10.1016/S0140-6736(16)00561-4. View