8 research outputs found
Biodiversity accounting and reporting: A systematic literature review and bibliometric analysis
Towards the improvement of environmental sustainability and the conservation of biodiversity, organisations are increasingly aware of the importance of reporting their impacts on biodiversity and the conservation plans undertaken. Biodiversity accounting and reporting are relevant for developing organisational practices oriented towards environmental sustainability, promoting cleaner management policies with less impact on the environment. Biodiversity accounting research has attracted scholars in business management and accounting, and as a result, the literature in the field has grown in recent years. This study analyses the intellectual structure of the biodiversity accounting and management discipline through a systematic literature review, along with bibliometric techniques based on a co-word analysis of the main keywords included in 63 publications. The results reveal five thematic clusters: one motor cluster (sustainability), two transversal clusters (biodiversity reporting, corporate biodiversity management) and two isolated clusters (environmental protection, emancipatory accounting). In addition, the content of the selected papers is analysed and promising research paths are found, such as the need for more robust quantitative analyses or the development of new forms of emancipatory accounting. The study discusses the main insights from the analysis, proposes future research directions and provides practical implications for biodiversity protection and environmental sustainability. © The Author
Human CD8 T cells are susceptible to TNF-mediated activation-induced cell death
Activation-induced cell death (AICD) is a complex immunoregulatory mechanism that causes the demise of a
fraction of T-lymphocytes upon antigen-driven activation. In the present study we investigated the direct role
of TNF in AICD of CD8 T lymphocytes.
Methods: Human peripheral mononuclear cells were isolated from healthy donors
and fresh tumor-infiltrating lymphocytes were obtained from cancer patients undergoing surgery. T cells were
activated with anti-CD3/CD28 mAbs or with a pool of virus peptides, in combination with clinicalgrade TNF blocking agents.
Results: A portion of CD8 T cells undergoes apoptosis upon CD3/CD28 activation in a manner that is partially
prevented by the clinically used anti-TNF agents infliximab and etanercept. TNF-mediated AICD was also
observed upon activation of virus-specific CD8 T cells and tumor-infiltrating CD8 T lymphocytes. The
mechanism of TNF-driven T cell death involves TNFR2 and production of mitochondrial oxygen free radicals
which damage DNA.
Conclusion: The use of TNF blocking agents reduces oxidative stress, hyperpolarization of mitochondria, and
the generation of DNA damage in CD8 T celss undergoing activation. The fact that TNF mediates AICD in
human tumor-reactive CD8 T cells suggests that the use of TNF-blocking agents can be exploited in
immunotherapy strategies
Human CD8 T cells are susceptible to TNF-mediated activation-induced cell death
Activation-induced cell death (AICD) is a complex immunoregulatory mechanism that causes the demise of a
fraction of T-lymphocytes upon antigen-driven activation. In the present study we investigated the direct role
of TNF in AICD of CD8 T lymphocytes.
Methods: Human peripheral mononuclear cells were isolated from healthy donors
and fresh tumor-infiltrating lymphocytes were obtained from cancer patients undergoing surgery. T cells were
activated with anti-CD3/CD28 mAbs or with a pool of virus peptides, in combination with clinicalgrade TNF blocking agents.
Results: A portion of CD8 T cells undergoes apoptosis upon CD3/CD28 activation in a manner that is partially
prevented by the clinically used anti-TNF agents infliximab and etanercept. TNF-mediated AICD was also
observed upon activation of virus-specific CD8 T cells and tumor-infiltrating CD8 T lymphocytes. The
mechanism of TNF-driven T cell death involves TNFR2 and production of mitochondrial oxygen free radicals
which damage DNA.
Conclusion: The use of TNF blocking agents reduces oxidative stress, hyperpolarization of mitochondria, and
the generation of DNA damage in CD8 T celss undergoing activation. The fact that TNF mediates AICD in
human tumor-reactive CD8 T cells suggests that the use of TNF-blocking agents can be exploited in
immunotherapy strategies
Repurposing the yellow fever vaccine for intratumoral immunotherapy
Live 17D is widely used as a prophylactic vaccine strain for yellow
fever virus that induces potent neutralizing humoral and cellular
immunity against the wild-type pathogen. 17D replicates and kills
mouse and human tumor cell lines but not non-transformed
human cells. Intratumoral injections with viable 17D markedly
delay transplanted tumor progression in a CD8 T-cell-dependent
manner. In mice bearing bilateral tumors in which only one is
intratumorally injected, contralateral therapeutic effects are
observed consistent with more prominent CD8 T-cell infiltrates
and a treatment-related reduction of Tregs. Additive efficacy
effects were observed upon co-treatment with intratumoral 17D
and systemic anti-CD137 and anti-PD-1 immunostimulatory monoclonal antibodies. Importantly, when mice were preimmunized
with 17D, intratumoral 17D treatment achieved better local and
distant antitumor immunity. Such beneficial effects of prevaccination are in part explained by the potentiation of CD4 and CD8
T-cell infiltration in the treated tumor. The repurposed use of a
GMP-grade vaccine to be given via the intratumoral route in
prevaccinated patients constitutes a clinically feasible and safe
immunotherapy approach
Cellular cytotoxicity is a form of immunogenic cell death
Background The immune response to cancer is often
conceptualized with the cancer immunity cycle. An essential
step in this interpretation is that antigens released by dying
tumors are presented by dendritic cells to naive or memory
T cells in the tumor-draining lymph nodes. Whether tumor
cell death resulting from cytotoxicity, as mediated by T cells
or natural killer (NK) lymphocytes, is actually immunogenic
currently remains unknown.
Methods In this study, tumor cells were killed by antigenspecific T-cell receptor (TCR) transgenic CD8 T cells or
activated NK cells. Immunogenic cell death was studied
analyzing the membrane exposure of calreticulin and the
release of high mobility group box 1 (HMGB1) by the dying
tumor cells. Furthermore, the potential immunogenicity of the
tumor cell debris was evaluated in immunocompetent mice
challenged with an unrelated tumor sharing only one tumorassociated antigen and by class I major histocompatibility
complex (MHC)-multimer stainings. Mice deficient in
Batf3, Ifnar1 and Sting1 were used to study mechanistic
requirements.
Results We observe in cocultures of tumor cells and effector
cytotoxic cells, the presence of markers of immunogenic
cell death such as calreticulin exposure and soluble HMGB1
protein. Ovalbumin (OVA)-transfected MC38 colon cancer
cells, exogenously pulsed to present the gp100 epitope are
killed in culture by mouse gp100-specific TCR transgenic
CD8 T cells. Immunization of mice with the resulting
destroyed cells induces epitope spreading as observed by
detection of OVA-specific T cells by MHC multimer staining
and rejection of OVA+
EG7 lymphoma cells. Similar results
were observed in mice immunized with cell debris generated
by NK-cell mediated cytotoxicity. Mice deficient in Batf3-
dependent dendritic cells (conventional dendritic cells type 1,
cDC1) fail to develop an anti-OVA response when immunized
with tumor cells killed by cytotoxic lymphocytes. In line with
this, cultured cDC1 dendritic cells uptake and can readily
cross-present antigen from cytotoxicity-killed tumor cells to
cognate CD8+
T lymphocytes.
Conclusion These results support that an ongoing
cytotoxic antitumor immune response can lead to
immunogenic tumor cell death
Repurposing the yellow fever vaccine for intratumoral immunotherapy
Live 17D is widely used as a prophylactic vaccine strain for yellow
fever virus that induces potent neutralizing humoral and cellular
immunity against the wild-type pathogen. 17D replicates and kills
mouse and human tumor cell lines but not non-transformed
human cells. Intratumoral injections with viable 17D markedly
delay transplanted tumor progression in a CD8 T-cell-dependent
manner. In mice bearing bilateral tumors in which only one is
intratumorally injected, contralateral therapeutic effects are
observed consistent with more prominent CD8 T-cell infiltrates
and a treatment-related reduction of Tregs. Additive efficacy
effects were observed upon co-treatment with intratumoral 17D
and systemic anti-CD137 and anti-PD-1 immunostimulatory monoclonal antibodies. Importantly, when mice were preimmunized
with 17D, intratumoral 17D treatment achieved better local and
distant antitumor immunity. Such beneficial effects of prevaccination are in part explained by the potentiation of CD4 and CD8
T-cell infiltration in the treated tumor. The repurposed use of a
GMP-grade vaccine to be given via the intratumoral route in
prevaccinated patients constitutes a clinically feasible and safe
immunotherapy approach
mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy
Interleukin-12 (IL-12) gene transfer enhances the therapeutic potency of adoptive T cell therapies. We previ-ously reported that transient engineering of tumor-specific CD8 T cells with IL-12 mRNA enhanced their sys-temic therapeutic efficacy when delivered intratumorally. Here, we mix T cells engineered with mRNAs to ex-press either single-chain IL-12 (scIL-12) or an IL-18 decoy-resistant variant (DRIL18) that is not functionally hampered by IL-18 binding protein (IL-18BP). These mRNA-engineered T cell mixtures are repeatedly in-jected into mouse tumors. Pmel-1 T cell receptor (TCR)-transgenic T cells electroporated with scIL-12 or DRIL18 mRNAs exert powerful therapeutic effects in local and distant melanoma lesions. These effects are associated with T cell metabolic fitness, enhanced miR-155 control on immunosuppressive target genes, enhanced expression of various cytokines, and changes in the glycosylation profile of surface proteins, enabling adhesiveness to E-selectin. Efficacy of this intratumoral immunotherapeutic strategy is recapitu-lated in cultures of tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T cells on IL -12 and DRIL18 mRNA electroporation