A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer

Abstract

Murine tissues harbor signature γδ T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident γδ cells are less well defined. In the present study, we show that human lung tissues harbor a resident Vδ1 γδ T cell population. Moreover, we demonstrate that Vδ1 T cells with resident memory and effector memory phenotypes were enriched in lung tumors compared with nontumor lung tissues. Intratumoral Vδ1 T cells possessed stem-like features and were skewed toward cytolysis and helper T cell type 1 function, akin to intratumoral natural killer and CD8+ T cells considered beneficial to the patient. Indeed, ongoing remission post-surgery was significantly associated with the numbers of CD45RA−CD27− effector memory Vδ1 T cells in tumors and, most strikingly, with the numbers of CD103+ tissue-resident Vδ1 T cells in nonmalignant lung tissues. Our findings offer basic insights into human body surface immunology that collectively support integrating Vδ1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer.

γδ T cells are effectors of immunotherapy in cancers with HLA class I defects

“…Different subsets of γδ T cells exhibit substantially diverse functions that, in the context of cancer, range from tumour-promoting to tumouricidal effects 20 , 28 , 29 . Thus, it is of interest to determine what defines antitumour reactivity of γδ T cells.…”

A close look at current γδ T-cell immunotherapy

“…The relationship between gd T cells and cancer prognosis is influenced by factors such as the pathological type of cancer (31), the gd T-cell subset (32), the time of sample harvesting (33), and the functioning state of the gd T cells (34). Clinical prognosis studies typically involve the analysis of either peripheral gd T cells or tumor-infiltrating gd T cells, and common methods include flow cytometry (35), immunohistochemistry (31,36), and gene expression measurement (34,37). Early studies often measured peripheral gd T cells without distinguishing subsets (38), whereas later studies began to analyze subsets separately (35).…”

Leveraging the Dynamic Immune Environment Triad in Patients with Breast Cancer: Tumour, Lymph Node, and Peripheral Blood

“…In this model, IL-17-producing γδ-T cells express IL-10, IL-8 and CD73, dampen naïve and effector T cell responses and proliferation, and block DC maturation and function [ 21 , 22 ]. Nonetheless, IL-17-producing γδ-T cells have been exceptionally hard to find in humans [ 20 , 40 ] and their potential to mount immune responses, independent of MHC-activation, make γδ-T cells attractive targets for “off-the-shelf” immunotherapy for breast and other cancers.…”