Maartje Wouters

The global response to COVID-19 has demonstrated the importance of vigilance and preparedness for infectious diseases, particularly influenza. There is a need for more effective influenza vaccines and modern manufacturing technologies that are adaptable and scalable to meet demand during a pandemic. The rapid development of COVID-19 vaccines has demonstrated what is possible with extensive data sharing, researchers who have the necessary resources and novel technologies to conduct and apply t...

Last week, the ACIR team attended the AACR Annual Meeting 2022 in New Orleans, LA. This week’s extensive special feature covers select talks from the conference.

Pancreatic ductal adenocarcinoma (PDAC) poses challenges for immunotherapy due to its low immunogenicity and highly immunosuppressive environment. To overcome these issues, Selvanesan, Chandra, and Quispe-Tintaya et al. developed a microbial-based treatment to deliver an immunogenic protein into tumor cells to trigger antitumor responses. Their results were recently published in Science Translational Medicine.

Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) signaling stimulates T cell activation and proliferation and can inhibit suppressive effects of regulatory T cells (Treg). However, agonistic GITR antibodies have shown limited results in the clinic, which may be due to limited receptor clustering-mediated signaling of this TNFR superfamily member. Therefore, Chan and Belmar et al. developed a protein engineering approach to improve GITR clustering and efficacy.

While tertiary lymphoid structures (TLS), organized lymphoid structures found in sites of chronic inflammation and antigen exposure, have been implicated in improved outcome and response to immunotherapy in cancer, the role of B cell responses associated with these structures is not well known. Therefore, Meylan et al. studied the role of TLS on B cell responses in the tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) using spatial transcriptomics, RNAseq, and multicolor...

Immunologically cold tumors generally respond poorly to immune checkpoint blockade (ICB). Defining the mechanisms that can increase immune infiltration into these tumors is essential to improving ICB therapy efficacy. Cisplatin chemotherapy treatment has been shown to synergize with ICB by increasing immune cell infiltration in cold tumors, but the mechanisms behind this remain unclear. Therefore, Bruchard et al. set out to answer this question using various animal models.

Migration to and invasion of solid tumor tissue by lymphocytes is essential for antitumor immunity and response to virtually any type of immunotherapy. However, the mechanisms by which lymphocytes enter tumors through vasculature remain largely unclear. Therefore, Asrir, Tardiveau, Coudert, Laffont, and Blanchard et al. studied high endothelial vessels (HEVs) – specialized blood vessels for lymphocyte recruitment in lymphoid organs – in various tumor models.

CAR T cell treatment (CAR-T) can be effective in hematological cancers, but is frequently associated with cytokine release syndrome (CRS), a severe adverse event. IFNγ has been implicated as a driving factor in the development of CRS, but is also considered essential for the efficacy of the treatment. Bailey et al. investigated how IFNγ blockade, using antibodies or deletion of IFNγ in CAR-T, affected treatment efficacy and whether it could prevent CRS.

In November, the ACIR team attended the SITC Annual Meeting 2021. This week’s extensive special feature covers select talks from the conference. We have organized the content by topics below.

Many non-small cell lung cancer (NSCLC) tumors do not respond to immune checkpoint blockade (ICB), even in the presence of CD8+ tumor-infiltrating lymphocytes (TILs). To explore the mechanisms behind this phenomenon, Horton et al. evaluated T cell phenotypes and functions in orthotopic lung and flank mouse models for NSCLC. Their results were recently published in Science Immunology.

In October, the ACIR team attended the virtual AACR Tumor Immunology and Immunotherapy conference 2021. This week’s extensive special feature covers select talks from the conference. We have organized the content by topics below.

While the effects of immune checkpoint blockade on the tumor microenvironment (TME) are widely investigated, the combined effect of chemotherapy and checkpoint blockade is less clear. Further, although the Impassion130 trial in advanced triple-negative breast cancer (TNBC) combining nab-paclitaxel with anti-PD-L1 therapy led to clear patient benefits and product approval, a similar trial (Impassion131) combining paclitaxel with anti-PD-L1 therapy did not, indicating that important distinction...

Human cytomegalovirus (HCMV) infection can have long-term immune effects, and NK and T cells both play roles in keeping HCMV latent. Based on the knowledge that CD8+ T cells can display NK cell-like properties, and that these cells can have a beneficial presence in individuals infected with particular intracellular pathogens causing tuberculosis or leprosy, Sottile et al. investigated this subset and determined the phenotype, transcriptomics, and reactivity of NKG2C+CD8+ T cells after HCMV ex...

Treatment of tumors with cytokines to boost antitumor immune responses is limited in the clinic due to systemic adverse events. Intratumoral delivery of cytokines may overcome these issues and improve therapeutic efficacy. Hotz and Wagenaar et al. thoroughly investigated the efficacy of local delivery of mRNA encoding a mixture of cytokines alone or combined with checkpoint blockade in murine models to take advantage of these powerful immune stimulants.

Since radiotherapy (RT) can boost immune priming, it can be a great tool to convert immune “cold” tumors into “hot” immune environments, making way for effective checkpoint inhibition therapies. However, RT may also remodel the tumor microenvironment (TME), creating barriers to immune infiltration and antitumor effects. Given that one of the main contributors to TME remodeling is the TGFβ pathway, combining RT with neutralization of TGFβ and checkpoint blockade may effectively treat cold tumo...