Biology subjects

Pommier, A.

Publications and source records attributed to Pommier, A..

4 recordsLinked to original sources

bioRxiv2018

Cancer cell CCR2 orchestrates suppression of the adaptive immune response

C-C chemokine receptor type 2 (CCR2) is expressed on monocytes and facilitates their recruitment to tumors. Though breast cancer cells also express CCR2, its functions in these cells are unclear. We found that Ccr2 deletion in cancer cells led to reduced tumor growth and [~]2-fold longer survival in an orthotopic, isograft breast cancer mouse model. Deletion of Ccr2 in cancer cells resulted in multiple alterations associated with better immune control: increased infiltration and activation of cytotoxic T lymphocytes (CTLs) and CD103+ cross-presenting dendritic cells (DCs), as well as upregulation of MHC class I and downregulation of checkpoint regulator PD-L1 on the cancer cells. Pharmacological or genetic targeting of CCR2 increased cancer cell sensitivity to CTLs and enabled the cancer cells to induce DC maturation toward the CD103+ subtype. Consistently, Ccr2-/- cancer cells did not induce immune suppression in Batf3-/- mice lacking CD103+ DCs. Our results establish that CCR2 signaling in cancer cells can orchestrate suppression of the immune response. SummaryC-C chemokine receptor type 2 (CCR2) expressed on monocytes facilitates their recruitment to tumors. Here, CCR2 signaling in cancer cells is shown to suppress immune control of tumors, in part by reducing CD103+ dendritic cell recruitment.

cancer biology↗

bioRxiv2018

Transcriptional plasticity evolution in two strains of Spodoptera frugiperda (Lepidoptera: Noctuidae) feeding on alternative host-plants

AO_SCPLOWBSTRACTC_SCPLOWSpodoptera frugiperda, the fall armyworm (FAW), is an important agricultural pest in the Americas and an emerging pest in sub-Saharan Africa, India, East-Asia and Australia, causing damage to major crops such as corn, sorghum and soybean. While FAW larvae are considered polyphagous, differences in diet preference have been described between two genetic variants: the corn strain (sf-C) and the rice strain (sf-R). These two strains are sometimes considered as distinct species, raising the hypothesis that ost plant specialization might have driven their divergence. To test this hypothesis, we irst performed controlled reciprocal transplant (RT) experiments to address the impact of plant diet on several traits linked to the fitness of the sf-C and sf-R strains. The phenotypical data suggest that sf-C is specialized to corn. We then used RNA-Se to identify constitutive transcriptional differences between strains, regardless of diet, in laboratory as well as in natural populations. We found that variations in mitochon rial transcription levels are among the most substantial and consistent differences between the two strains. Since mitochondrial genotypes also vary between the strains, we believe the mitochondria may have a significant role in driving strain divergence.

evolutionary biology↗

bioRxiv2018

Transcriptomic response to host and non-host plants during oviposition in two closely related moth species

We present here a comprehensive analysis of the transcriptomic response to plant environments in ovipositing females of two sibling species of phytophagous moths affiliated to different host ranges: the European corn borer (ECB) and the adzuki bean borer (ABB). We first assembled and annotated a de novo reference transcriptome based on a high throughput RNA sequencing of females placed in different plant environments, then we measured differences in gene expression between ECB and ABB, and also within each moth species between environments. We further related the differentially expressed (DE) genes to the host preference in ECB and ABB and highlighted the functional categories involved. More specifically, we conducted an analysis on chemosensory genes previously characterized in ECB, ABB and other related Ostrinia species, as these genes are considered as good candidates for the host recognition before oviposition.\n\nOverall, we recorded more DE genes in ECB than in ABB samples, what could highlight the higher strength of the host specialization in ECB compared to ABB as observed at the behavioral level. We also noticed that the genes involved in the preference for their respective host were different between ECB and ABB. At the functional level, the response to plant environment in ECB and ABB during oviposition involved many processes, including the chemosensory repertoire as expected, but also metabolism of carbohydrates, lipids, proteins, and amino acids, detoxification mechanisms and immunity.\n\nAll together, our results allowed identifying genes and functions candidates for specialization and also for the species divergence between ECB and ABB. By ad-hoc categorization, we discriminated some genes responding to the environment with similar or divergent pattern in ECB and ABB. Among them, we highlighted new lines of research like carbohydrates metabolism or virus and retrovirus dynamics.

evolutionary biology↗

bioRxiv2017

Endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases

Patients who have had their primary pancreatic ductal adenocarcinoma (PDA) surgically resected often develop metastatic disease, exemplifying the problem of latent metastases. Livers from patients and mice with PDA contained single, disseminated cancer cells (DCCs) with an unusual phenotype of being cytokeratin-19 (CK19)- and MHC class I (MHCI)-. We created a mouse model to determine how DCCs develop, their relationship to metastatic latency, and the role of immunity. Intra-portal injection of immunogenic PDA cells into pre-immunized mice seeded livers only with single, non-replicating DCCs lacking MHCI and CK19; naive recipients had macro-metastases. Transcriptomic analysis of PDA cells with the DCC phenotype demonstrated an endoplasmic reticulum (ER) stress response. Relieving ER stress with a chemical chaperone, in combination with T cell-depletion, stimulated outgrowth of macro-metastatic lesions containing PDA cells expressing MHCI and CK19. The ER stress response is the cell-autonomous reaction that enables DCCs to escape immunity and establish latent metastases.\n\nOne sentence summaryLatent pancreatic cancer metastases are created when T cells select disseminated cancer cells in which immune resistance and quiescence have been imposed by endoplasmic stress.

immunology↗