Evolution of Large Eyes in Stromboidea (Gastropoda): Impact of Photic Environment and Life History Traits.

Eyes within the marine gastropod superfamily Stromboidea range widely in size, from 0.2 to 2.3 mm - the largest eyes known in any gastropod.

A reporter virus particle seroneutralization assay for tick-borne encephalitis virus overcomes ELISA limitations.

Tick-borne encephalitis (TBE) virus is the most prevalent tick-transmitted orthoflavivirus in Europe. Due to the nonspecific nature of its symptoms, TBE is primarily diagnosed by ELISA-based detection of specific antibodies in the patient serum. However, cross-reactivity between orthoflaviviruses complicates the diagnosis.

A tetravalent nanovaccine that inhibits growth of HPV-associated head and neck carcinoma via dendritic and T cell activation.

The global incidence of human papillomavirus (HPV) associated head and neck carcinoma is on the rise, in response to this a tetravalent therapeutic vaccine named Qβ-HPVag was developed. This vaccine, utilizing virus-like particles (VLPs) loaded with toll-like receptor ligands and chemically coupled to four HPV16-derived peptides, demonstrated strong anti-tumor effects in a murine head and neck cancer model. Qβ-HPVag impeded tumor progression, increased infiltration of HPV-specific T cells, and significantly improved survival.

Immunopeptidomics-based identification of naturally presented non-canonical circRNA-derived peptides.

Circular RNAs (circRNAs) are covalently closed non-coding RNAs lacking the 5' cap and the poly-A tail. Nevertheless, it has been demonstrated that certain circRNAs can undergo active translation. Therefore, aberrantly expressed circRNAs in human cancers could be an unexplored source of tumor-specific antigens, potentially mediating anti-tumor T cell responses.

A morphological basis for path-dependent evolution of visual systems.

Path dependence influences macroevolutionary predictability by constraining potential outcomes after critical evolutionary junctions. Although it has been demonstrated in laboratory experiments, path dependence is difficult to demonstrate in natural systems because of a lack of independent replicates. Here, we show that two types of distributed visual systems recently evolved twice within chitons, demonstrating rapid and path-dependent evolution of a complex trait.

Successful Allergen-Specific Immunotherapy: Induction of Unresponsiveness by 'Vaccination'.

The mechanisms of action of allergen-specific immunotherapy (AIT) are often referred to as the induction of 'tolerance'. However, immunological 'tolerance' is defined as an alteration in the function or composition of immune cells. For AIT, this is not always the case, because it can also induce allergen-specific IgG antibodies that block allergic responses.

Regulatory circuits of mitophagy restrict distinct modes of cell death during memory CD8 T cell formation.

Mitophagy, a central process guarding mitochondrial quality, is commonly impaired in human diseases such as Parkinson's disease, but its impact in adaptive immunity remains unclear. The differentiation and survival of memory CD8 T cells rely on oxidative metabolism, a process that requires robust mitochondrial quality control. Here, we found that Parkinson's disease patients have a reduced frequency of CD8 memory T cells compared with healthy donors and failed to form memory T cells upon vaccination against COVID-19, highlighting the importance of mitochondrial quality control for memory CD8 T cell formation.

A phase 1 trial of adoptive transfer of vaccine-primed autologous circulating T cells in ovarian cancer.

We have previously shown that vaccination with tumor-pulsed dendritic cells amplifies neoantigen recognition in ovarian cancer. Here, in a phase 1 clinical study ( NCT01312376 /UPCC26810) including 19 patients, we show that such responses are further reinvigorated by subsequent adoptive transfer of vaccine-primed, ex vivo-expanded autologous peripheral blood T cells. The treatment is safe, and epitope spreading with novel neopeptide reactivities was observed after cell infusion in patients who experienced clinical benefit, suggesting reinvigoration of tumor-sculpting immunity.

Combinatorial Treatment with PARP and MAPK Inhibitors Overcomes Phenotype Switch-Driven Drug Resistance in Advanced Melanoma.

Unlabelled: Metastatic melanoma is either intrinsically resistant or rapidly acquires resistance to targeted therapy treatments, such as MAPK inhibitors (MAPKi). A leading cause of resistance to targeted therapy is a dynamic transition of melanoma cells from a proliferative to a highly invasive state, a phenomenon called phenotype switching. Mechanisms regulating phenotype switching represent potential targets for improving treatment of patients with melanoma.

Activation of the transcription factor NFAT5 in the tumor microenvironment enforces CD8 T cell exhaustion.

Persistent exposure to antigen during chronic infection or cancer renders T cells dysfunctional. The molecular mechanisms regulating this state of exhaustion are thought to be common in infection and cancer, despite obvious differences in their microenvironments. Here we found that NFAT5, an NFAT family transcription factor that lacks an AP-1 docking site, was highly expressed in exhausted CD8 T cells in the context of chronic infections and tumors but was selectively required in tumor-induced CD8 T cell exhaustion.

Two sides of the same wing: ventral scales enhance dorsal wing color in the butterfly Speyeria mormonia.

Biological visual signals are often produced by complex interactions between light-absorbing and light-scattering structures, but for many signals, potential interactions between different light-interacting components have yet to be tested. Butterfly wings, for example, are thin enough that their two sides may not be optically isolated. We tested whether ventral wing scales of the Mormon fritillary, Speyeria mormonia, affect the appearance of dorsal orange patches, which are thought to be involved in sexual signaling.

Clonal expansion of intra-epithelial T cells in breast cancer revealed by spatial transcriptomics.

The spatial distribution of tumor-infiltrating lymphocytes (TIL) predicts breast cancer outcome and response to systemic therapy, highlighting the importance of an intact tissue structure for characterizing tumors. Here, we present ST-FFPE, a spatial transcriptomics method for the analysis of formalin-fixed paraffin-embedded samples, which opens the possibility of interrogating archival tissue. The method involves extraction, exome capture and sequencing of RNA from different tumor compartments microdissected by laser-capture, and can be used to study the cellular composition of tumor microenvironment.

Neoantigen-specific CD8 T cells with high structural avidity preferentially reside in and eliminate tumors.

The success of cancer immunotherapy depends in part on the strength of antigen recognition by T cells. Here, we characterize the T cell receptor (TCR) functional (antigen sensitivity) and structural (monomeric pMHC-TCR off-rates) avidities of 371 CD8 T cell clones specific for neoantigens, tumor-associated antigens (TAAs) or viral antigens isolated from tumors or blood of patients and healthy donors. T cells from tumors exhibit stronger functional and structural avidity than their blood counterparts.

TCR sequencing and cloning methods for repertoire analysis and isolation of tumor-reactive TCRs.

T cell receptor (TCR) technologies, including repertoire analyses and T cell engineering, are increasingly important in the clinical management of cellular immunity in cancer, transplantation, and other immune diseases. However, sensitive and reliable methods for repertoire analyses and TCR cloning are still lacking. Here, we report on SEQTR, a high-throughput approach to analyze human and mouse repertoires that is more sensitive, reproducible, and accurate as compared with commonly used assays, and thus more reliably captures the complexity of blood and tumor TCR repertoires.

IL-18 and VEGF-A trigger type 2 innate lymphoid cell accumulation and pro-tumoral function in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a hematologic malignancy associated to an unregulated growth of myeloid cells in bone marrow (BM) and peripheral blood (PB), characterized by the BCR-ABL1 translocation. Given the known cytokine impairment in the leukemic niche of CML, we investigated the impact of this microenvironmental dysregulation on innate lymphoid cells (ILC), whose role in cancer has recently emerged. Three ILC subsets are identified based on transcriptional profiles and cytokine secretion.

CD4 T cells in cancer.

Cancer immunology and immunotherapy are driving forces of research and development in oncology, mostly focusing on CD8 T cells and the tumor microenvironment. Recent progress highlights the importance of CD4 T cells, corresponding to the long-known fact that CD4 T cells are central players and coordinators of innate and antigen-specific immune responses. Moreover, they have now been recognized as anti-tumor effector cells in their own right.

Neoantigen-targeted CD8 T cell responses with PD-1 blockade therapy.

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells. The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy.

Vaccination using mutated receptor binding domains of SARS-CoV-2: Evidence for partial immune escape but not serotype formation.

Introduction: SARS-CoV-2 has developed a number of Variants of Concern (VOC) with increased infectivity and/or reduced recognition by neutralizing antibodies specific for the receptor binding domain (RBD) of the spike protein. Extended studies of other viruses have shown that strong and broad viral escape from neutralizing serum antibodies is typically associated with the formation of serotypes.

Methods: To address the question of serotype formation for SARS-CoV-2 in detail, we generated recombinant RBDs of VOCs and displayed them on virus-like particles (VLPs) for vaccination and specific antibody responses.

Polarization sensitivity and decentralized visual processing in an animal with a distributed visual system.

The marine mollusc Acanthopleura granulata (Mollusca; Polyplacophora) has a distributed visual array composed of hundreds of small image-forming eyes embedded within its eight dorsal shell plates. As in other animals with distributed visual systems, we still have a poor understanding of the visual capabilities of A. granulata and we have yet to learn where and how it processes visual information.

Dendritic cells direct circadian anti-tumour immune responses.

The process of cancer immunosurveillance is a mechanism of tumour suppression that can protect the host from cancer development throughout its lifetime. However, it is unknown whether the effectiveness of cancer immunosurveillance fluctuates over a single day. Here we demonstrate that the initial time of day of tumour engraftment dictates the ensuing tumour size across mouse cancer models.

Peroxynitrite in the tumor microenvironment changes the profile of antigens allowing escape from cancer immunotherapy.

Cancer immunotherapy often depends on recognition of peptide epitopes by cytotoxic T lymphocytes (CTLs). The tumor microenvironment (TME) is enriched for peroxynitrite (PNT), a potent oxidant produced by infiltrating myeloid cells and some tumor cells. We demonstrate that PNT alters the profile of MHC class I bound peptides presented on tumor cells.

In situ delivery of nanoparticles formulated with micron-sized crystals protects from murine melanoma.

Introduction: Intratumoral injections of novel therapeutics can activate tumor antigen-specific T cells for locoregional tumor control and may even induce durable systemic protection (against distant metastases) via recirculating T cells. Here we explored the possibility of a universal immunotherapy that promotes T-cell responses in situ and beyond, upon intratumoral injection of nanoparticles formulated with micron-sized crystals.

Methods: Cucumber mosaic virus-like particles containing a tetanus toxin peptide (CuMV) were formulated with microcrystalline tyrosine (MCT) adjuvant and injected directly in B16F10 melanoma tumors.