Search

Immune checkpoint blockade has shown clinical activity in a range of cancer types. To dissect the effect of neoadjuvant PD-1 and CTLA4 blockade on intratumoral T cells in head and neck squamous cell carcinoma, we analyzed immune infiltrates in tumor biopsies from responding and non-responding patients. At baseline, a higher ratio between active (4-1BB+) and inactive regulatory CD4+ T cells was associated with response to therapy. Furthermore, upon therapy, this active Treg population showed a profound decrease in responding patients. In an analogous process, intratumoral dysfunctional CD8+ T cells transitioned to a state of reduced activity and dysfunction in responding patients, while in non-responding patients, NK cells showed an increased cytotoxic transcriptional profile upon treatment. These data reveal the immunological changes in response to dual PD-1 and CTLA4 blockade, including a parallel remodeling of presumed tumor-reactive T cell compartments in responding patients, and indicate that the presence of an activated Treg compartment at baseline may predict response. Citation Format: Anne M. van der Leun, Joleen J. Traets, Joris L. Vos, Joris B. Elbers, Sanne Patiwael, Xiaohang Qiao, Mercedes Machuca-Ostos, Daniela S. Thommen, John B. Haanen, Ton N. Schumacher, Charlotte L. Zuur. Dual immune checkpoint blockade induces analogous alterations in the dysfunctional CD8+ T cell and activated Treg compartment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2281.

Intratumoral T cell composition is relevant for disease outcome across tumor types

The T cell infiltrates that are formed in human cancers are a modifier of natural disease progression and also determine the probability of clinical response to cancer immunotherapies. Recent technological advances that enable the single-cell analysis of phenotypic and transcriptional states have revealed a vast heterogeneity of intratumoral T cell states, both within and between patients, and the observation of this heterogeneity makes it critical to understand the relationship between individual T cell states and therapy response. This Review covers our current knowledge regarding the T cell states that are present in human tumors and the role that different T cell populations have been hypothesized to play within the tumor microenvironment, with a particular focus on CD8(+) T cells. Three key models that are discussed herein are: 1). The dysfunction of T cells in human cancer is associated with a change in T cell functionality rather than inactivity; 2). Antigen recognition in the tumor microenvironment is an important driver of T cell dysfunctionality and the presence of dysfunctional T cells can hence be used as a proxy for the presence of a tumor-reactive T cell compartment; 3). A less dysfunctional population of tumor-reactive T cells may be required to drive a durable response to T cell immune checkpoint blockade.

Contains fulltext : 108069.pdf (Publisher’s version ) (Open Access) The plasmacytoid dendritic cell (pDC) constitutes a unique DC subset that links the innate and adaptive arm of the immune system. Whereas the unique capability of pDCs to produce large amounts of type I IFNs in response to pathogen recognition is generally accepted,their antigen-presenting function is often neglected since most studies on antigen presentation are aimed at other DC subsets. Recently, pDCs were demonstrated capable to present antigen leading to protective tumor immunity. In this review, we discuss how pDCs could be exploited in the fight against cancer by analyzing their capacity to capture,process and (cross-) present antigen.