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Objectives With the ongoing emergence of SARS‐CoV‐2 variants and potential to evade vaccine‐induced neutralisation, understanding the magnitude and breadth of vaccine‐induced T‐cell immunity will be critical for the ongoing optimisation of vaccine approaches. Strategies that provide a rapid and easily translatable means of assessing virus‐specific T‐cell responses provide an opportunity to monitor the impact of vaccine rollouts in the community. In this study, we assessed whether our recently developed SARS‐CoV‐2 whole‐blood assay could be used effectively to analyse T‐cell responses following vaccination. Methods Following a median of 15 days after the first dose of the ChAdOx1‐S (AstraZeneca®) vaccine, peripheral blood was isolated from 58 participants. Blood was incubated overnight with an overlapping set of spike protein peptides and assessed for cytokine production using a cytometric bead array. Results The majority of vaccine recipients (51/58) generated a T helper 1 response (IFN‐γ and/or IL‐2) following a single dose of ChAdOx1‐S. The magnitude of the IFN‐γ and IL‐2 response strongly correlated in vaccine recipients. While the production of other cytokines was evident in individuals who did not generate IFN‐γ and IL‐2, they showed no correlation in magnitude, nor did we see a correlation between sex or age and the magnitude of the response. Conclusions The whole‐blood cytokine assay provides a rapid approach to assessing T‐cell immunity against SARS‐CoV‐2 in vaccine recipients. While the majority of participants generated a robust SARS‐CoV‐2‐specific T‐cell response following their first dose, some did not, demonstrating the likely importance of the booster dose in improving T‐cell immunity., Strategies that provide a rapid and easily translatable means of assessing SARS‐CoV‐2‐specific T‐cell responses provide an opportunity to monitor the impact of vaccine rollouts in the community. In this study, we assessed whether our recently developed SARS‐CoV‐2 whole‐blood assay could be used effectively to analyse T‐cell responses following vaccination. We demonstrated that the whole‐blood cytokine assay provides a rapid approach to assessing T‐cell immunity against SARS‐CoV‐2 in vaccine recipients.

Objectives Clinical response to antibody‐based immunotherapies targeting checkpoint inhibitors is critically dependent on the tumor immune microenvironment (TIME). However, the precise impact of the TIME on adoptive cellular immunotherapy remains unexplored. Here we have conducted a long‐term follow‐up analysis of patients with recurrent glioblastoma multiforme (GBM) who were treated with autologous CMV‐specific T‐cell therapy to delineate the potential impact of the TIME on their clinical response. Methods Multiplexed immunohistochemical analysis of CD3, PD‐L1 and Sox‐2 in GBM tissue biopsies obtained before autologous T‐cell therapy was carried out and correlated with long‐term survival of GBM patients adoptively treated with T‐cell therapy. Results Tumor microenvironment analyses revealed that the pre‐treatment cellular composition of the tumor tissue may influence the subsequent response to adoptive T‐cell therapy. GBM patients who showed prolonged overall survival following T‐cell therapy had a significantly lower number of tumor‐infiltrating CD3+ T cells in recurrent tumors than that in patients with short‐term survival. Furthermore, long‐term surviving patients showed low or undetectable PD‐L1 expression in tumor cells in recurrent GBM biopsies. Conclusion We hypothesise that lack of PD‐L1‐mediated immunosuppression in the TIME may allow efficient immune control following adoptive T‐cell therapy. Future studies combining anti‐PD‐L1 or genetically modified T cells with PD‐1 receptor knockdown could be considered to improve clinical responses in patients who have high PD‐L1 expression in their tumors., The precise role of tumor immune microenvironment (TIME) on clinical response to adoptive cellular immunotherapies remains largely unexplored. In this paper, we have analysed the impact of TIME on the clinical response of glioblastoma patients who showed either long‐term or short‐term overall survival following adoptive T‐cell therapy.

[Extract] T cells play a central role in immunity as both regulators and effectors of immune function, following recognition of antigenic peptides presented by human leucocyte antigens (HLA) via the αβ T cell receptor (TCR). As such, the genes that encode the TCR have long been considered candidates for disease association. The human TCR is assembled from a total of 174 gene segments on chromosomes 7 and 14. Each α-chain is encoded by a variable (TRAV), a joining and a constant gene, while each β-chain is encoded by a variable (TRBV), a diversity, a joining and a constant gene (Davis & Bjorkman, 1988).

[Extract] In times of limited material, expansion of T cells in vitro has become a standard practice across many clinical and basic immunological procedures; such as haematopoietic stem cell transplantation, the study of biopsy specimens, immunomonitoring of clinical trial patients and the study of samples from neonates and children. Classically, mitogenic lectins, such as phytohaemagglutinin (PHA-P) or the phorbol esterphorbol 12-myristate 13-acetate, have been used for initiating T cell expansion. However, a more physiologically relevant method of T cell stimulation mimics the interaction with antigen-presenting cells through the use of anti-CD3 and anti-CD28 monoclonal antibodies (mAb) (Martin et al, 1986). This procedure has been improved in recent years, by fusing anti-CD3 and anti-CD28 mAb to microbead structures (Pene et al, 2003). Here, the initial signal is provided by CD3 molecule activation and the co-stimulatory signal is provided by CD28 molecule activation. In this study, we assessed whether human T-activator CD3/CD28 Dynabeads or PHA-P could amplify T cells from human umbilical cord blood (UCB) or adult peripheral blood mononuclear cells (PBMC) without distorting the baseline ex vivo T cell repertoire.