Deciphering the Roles of Innate Lymphoid Cells in Cancer

Cancer is a complex disease and the role played by innate lymphoid cells (ILCs) in cancer development has begun to be uncovered over recent years. We aim to provide an exhaustive summary of the knowledge acquired on the role of ILCs in cancer. ILCs are classified into 3 different categories, ILC1s, ILC2s, and ILC3s, each encompassing specific and unique functions. ILC1s exhibit NK cells characteristics and can exert anti-tumor functions, but surprisingly their IFNγ production is not associated with a better immune response. In response to TGF-β or IL-12, ILC1s were shown to exert pro-tumor functions and to favor tumor growth. ILC2s role in cancer immune response is dependent on cytokine context. The production of IL-13 by ILC2s is associated with a negative outcome in cancer. ILC2s can also produce IL-5, leading to eosinophil activation and an increased anti-tumor immune response in lung cancer. ILC3s produce IL-22, which could promote tumor growth. In contrast, ILC3s recognize tumor cells and facilitate leukocyte tumor entry, increasing anti-tumor immunity. In some contexts, ILC3s were found at the edge of tertiary lymphoid structures, associated with a good prognostic. We are at the dawn of our understanding of ILCs role in cancer. This review aims to thoroughly analyze existing data and to provide a comprehensive overview of our present knowledge on the impact of ILCs in cancer

Cooperating Teachers\u27 Perceived Preparedness to Support Science Teacher Candidates for Culturally Sustaining Science Teaching

In the United States, many communities face challenges that require science, technology, engineering, and math (STEM) solutions. Those communities most affected by these challenges often lack opportunities in school to use their funds of knowledge as they develop STEM literacies that would equip them to address these challenges. With new national science standards and increasingly diverse student demographics in classrooms across the United States, teacher educators must utilize strategies that prepare science teacher candidates, who are predominantly White, with pedagogies that can support diverse learners in expanding their STEM literacies from their funds of knowledge. The problem of practice guiding this research was that within the shifting landscape of STEM education, too few science teachers are prepared to implement the new standards in ways that are culturally sustaining for their traditionally underserved learners. The purpose of this convergent mixed methods study was to describe cooperating teachers\u27 perceived preparedness to support science teacher candidates to use culturally sustaining pedagogies to inform practices and policies that influence STEM teacher preparation. To address the problem of practice quantitative and qualitative data were collected using a survey instrument and then analyzed through the lens of a conceptual framework developed called culturally sustaining science teaching. The findings suggest cooperating teachers feel prepared for the components of the culturally sustaining science teaching framework (curriculum, instruction, and relationships). No statistically significant differences were shown between the components but nuanced differences were apparent when quantitative mean score ranks and qualitative data were converged

Regulation of T cell antitumor immune response by tumor induced metabolic stress

Adaptive T cell immune response is essential for tumor growth control. The efficacy of immune checkpoint inhibitors is regulated by intratumoral immune response. The tumor microenvironment has a major role in adaptive immune response tuning. Tumor cells generate a particular metabolic environment in comparison to other tissues. Tumors are characterized by glycolysis, hypoxia, acidosis, amino acid depletion and fatty acid metabolism modification. Such metabolic changes promote tumor growth, impair immune response and lead to resistance to therapies. This review will detail how these modifications strongly affect CD8 and CD4 T cell functions and impact immunotherapy efficacy

Chemoimmunotherapy triggers immune responses targeting microsatellite stable colorectal cancer

ABSTRACTCheckpoint blockade immunotherapy transforms many types of cancer; however, in the field of metastatic colorectal cancer, checkpoint blockers are only effective in microsatellite-unstable tumors, which represent only a minority of patients. Microsatellite-stable tumors are thought to be immunoresistant. A recent publication demonstrates that, contrary to the standard view point, the combination of chemo-immunotherapy could trigger a tumor-specific immune response, leading to clinical benefit

Sirolimus, bevacizumab, 5-Fluorouracil and irinotecan for advanced colorectal cancer: A pilot study

AIM: To evaluate the efficacy and the safety of combined 5-Fluorouracil, irinotecan, bevacizumab and sirolimus in refractory advanced colorectal carcinoma

Tumour mutational burden as a biomarker for immunotherapy: Current data and emerging concepts

International audienceTreatment with immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand (PD-L1) can generate durable responses in various cancer types, but only in a subset of patients. The use of predictive biomarkers for response to PD-1/PD-L1 inhibitors is critical for patient selection. Expression of PD-L1 has demonstrated utility in patient selection. Tumour mutational burden (TMB) is an emerging biomarker for response to PD-1/PD-L1 inhibitors. The evaluation of this biomarker is based on the hypothesis that a high number of mutations in somatic exonic regions will lead to an increase in neoantigen production, which could then be recognised by CD8+ T cells, resulting in improved immune responses. In this review, we will discuss rationale and implementation of TMB usage in patients, development of different methods to assess it, current limitations and technical issues to use this biomarker as a diagnostic test and propose future perspectives beyond TMB

Efficiency of olaparib in colorectal cancer patients with an alteration of the homologous repair protein.

International audiencePrecision medicine is defined by the administration of drugs based on the tumor's particular genetic characteristics. It is developing quickly in the field of cancer therapy. For example, KRAS, NRAS and BRAF genetic testing demonstrates its efficiency for precision medicine in colorectal cancer (CRC). Besides for these well-known mutations, the purpose of performing larger genetic testing in this pathology is unknown. Recent reports have shown that using the poly ADP ribose polymerase (PARP) inhibitor olaparib in patients with homologous repair enzyme deficiency gave positive clinical results in breast, ovarian and prostate cancers. We have reported here the cases of 2 patients with multi-treated metastatic CRC who underwent somatic and constitutional exome analyses. The analyses revealed a loss of function mutation in a homologous repair enzyme resulting in the loss of heterozygosity for both patients (Check2 for the first patient and RAD51C for the second one). Both patients were treated with off-label usage of olaparib. While the first patient showed clinical benefit, reduction of carcinoembryonic antigen tumor marker and radiologic response, the second patient quickly presented a progression of the tumor. Additional genetic analyses revealed a frameshift truncating mutation of the TP53BP1 gene in the patient who progressed. Interestingly, deficiency in TP53BP1 was previously described to confer resistance to olaparib in mice breast cancer models. Our findings suggest that exome analysis may be a helpful tool to highlight targetable mutations in CRC and that olaparib may be efficient in patients with a homologous repair deficiency

Comparison of different vehicles for tocopherols treatment of Caco-2 cells

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