Soumya Badrinath’s research while affiliated with Dana-Farber Cancer Institute and other places

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Publications (6)


Efficacy of the MICA/B α3 domain cancer vaccine
a, Design of the MICA/B vaccine. pAbs, polyclonal serum IgG. b, MICB-specific serum antibody (Ab) titres quantified by flow cytometry (n = 4 mice per group) in MICB-transgenic mice immunized with Ctrl-vax (blue) or MICB-vax (red). MFI, median fluorescence intensity. c, MICB-specific CD4⁺ T cell responses following immunization with MICB-vax or Ctrl-vax; CFSE dilution of splenocytes stimulated with MICB or control protein (ovalbumin (OVA)); shown are representative flow cytometry plots (left) and quantification for three mice per group (right). d, Cell-surface levels of MICB on B16F10 (MICB) tumours from mice immunized with MICB-vax or Ctrl-vax (n = 4 mice per group); staining of tumour cells with isotype-control monoclonal antibody (grey) or anti-MICA/B monoclonal antibody (specific for the α1–α2 domains, monoclonal antibody not blocked by vaccine-induced antibodies). e, Therapeutic efficacy of MICB-vax (red) or Ctrl-vax (blue) in mice with established B16F10 (MICB) tumours immunized at the indicated time points (n = 7 mice per group). Vax, vaccination. *P = 0.0137, ****P < 0.0001; NS (not significant), P > 0.999. f, g, Vaccine efficacy in two models of spontaneous metastasis. Mice were immunized with Ctrl-vax (blue) or MICB-vax (red) following surgical removal of primary tumours using the B16-B6 melanoma (f; 10 mice per group) or 4T1 breast cancer (g; 13 mice per group) models. Shown are the size of primary tumours at the time of surgery (left), representative images of lung metastases (middle) and quantification of the total number of lung surface metastases (right). D, day; s.c., subcutaneous. h, i, Immunogenicity of the rhesus MICA/B α3 domain vaccine in the rhesus macaque model. h, Timeline of vaccination; blood was drawn 24 h before indicated immunization or boost. i, Serum titres of antibody to rhesus MICA/B for animal ID 9312. Representative data are shown from at least three (b) or two (c–g) independent experiments. Data from a single experiment with technical replicates for each time point are shown in i. Statistical significance was assessed by two-tailed unpaired Student’s t test (b), two-way ANOVA with Sidak’s multiple-comparison test (c), one-way ANOVA with Tukey’s multiple-comparison test (d), two-way ANOVA with Bonferroni’s post hoc test (left) and the log-rank (Mantel–Cox) test (right) (e), two-tailed Mann–Whitney test (f, g) and two-way ANOVA with Tukey’s multiple-comparison test (i). Data are depicted as the mean ± s.e.m. (b–g) or mean ± s.d. (i).
Source data
Vaccine induces T cell and NK cell recruitment into tumours
a, Strategy for characterization of tumour-infiltrating immune cells by flow cytometry (FACS) and scRNA-seq. Mice received two immunizations (days 0 and 14), B16F10 (MICB-dox) tumour cells were implanted (day 21), MICB expression was induced on tumour cells by doxycycline treatment (day 28) and tumour-infiltrating immune cells were analysed 7 d later. b–d, Tumour-infiltrating T cell populations following immunization with Ctrl-vax (blue) or MICB-vax (red) (Ctrl-vax, n = 9 mice per group; MICB-vax, n = 10 mice per group; n = 7 mice per group for the γδ T cell panel). Treg cells, regulatory T cells. e, Tumour-infiltrating NK cells (n = 8 mice per group). f, g, Quantification of IFNγ-positive CD4⁺ and CD8⁺ T cells (Ctrl-vax, n = 9 mice per group; MICB-vax, n = 10 mice per group). h, i, UMAP representation of all T cell clusters from scRNA-seq data (h) and the fraction of each T cell subpopulation among total CD45⁺ cells from the experimental group (MICB-vax + doxycycline; red) and three combined control groups (Ctrl-vax ± doxycycline and MICB-vax without doxycycline; blue) (i). DN, double negative. j, k, UMAP representation of NK and ILC1 cells from all experimental groups (j) and the fraction of these subpopulations among total CD45⁺ cells from experimental (red) and combined control (blue) groups (k). l, Fraction of T cells representing expanded clones based on TCR sequence analysis for the experimental group (red) and combined control groups (blue). m, Contribution of CD4⁺ T cells, NK cells and NKG2D receptor to vaccine efficacy. Mice were first immunized with MICB-vax (M) or Ctrl-vax (C) (days 0 and 14) and treated with isotype-control monoclonal antibody (iso), depleting monoclonal antibody (targeting CD4⁺ T cells or NK cells (αCD4 and αNK1.1, respectively)) or NKG2D receptor-blocking monoclonal antibody (αNKG2D) starting on day 21, followed by implantation of B16F10 (MICB) tumour cells (n = 7 mice per group). Representative data from three independent experiments are shown in b–g. scRNA-seq data from a single experiment with sorted CD45⁺ cells pooled from five mice per group are shown in h–l. Representative data from two independent experiments are shown in m. Statistical significance was assessed by two-tailed Mann–Whitney test (b–g) or log-rank (Mantel–Cox) test (m). Data are depicted as the mean ± s.e.m.
Source data
Vaccine retains efficacy against MHC-I-deficient tumours
a, b, Comparison of vaccine efficacy against B16F10 (MICB) WT tumours and tumours with resistance mutations in the B2m (a) or Ifngr1 (b) gene. Mice received MICB-vax or Ctrl-vax and were then challenged with tumours of the indicated genotype (n = 7 mice per group). KO, knockout. c, Effect of CD4⁺ T cell and NK cell depletion on immunity to B2m-knockout tumours. Mice were immunized with MICB-vax or Ctrl-vax; treatment with depleting or isotype-control monoclonal antibody was started 2 d before injection of B2m-knockout B16F10 (MICB) tumour cells (n = 7 mice per group). d, Contribution of vaccine-induced anti-MICB antibodies to NK cell-mediated cytotoxicity against B2m-knockout B16F10 (MICB) tumour cells. CFSE-labelled B2m-knockout B16F10 (MICB) tumour cells were pre-incubated with 10 µg per well of purified serum IgG from mice immunized with MICB-vax or Ctrl-vax before the addition of NK cells at different effector to target (E:T) ratios as indicated. The percentage of dead target cells was assessed by flow cytometry. e, Effect of CD4⁺ T cell depletion on vaccine-induced NK cell infiltration into tumours. Flow cytometry quantification of total NK cell numbers is shown in WT (left) and B2m-knockout (right) tumours for the following treatment groups: Ctrl-vax + isotype-control monoclonal antibody (blue), Ctrl-vax + anti-CD4 (orange), MICB-vax + isotype-control monoclonal antibody (red) and MICB-vax + anti-CD4 (green) (n = 7 mice per group). Representative data from two independent experiments are shown in a–e. Statistical significance was assessed by two-way ANOVA with Bonferroni’s post hoc test (left) and log-rank (Mantel–Cox) test (right) (a–c), two-way ANOVA with Sidak’s multiple-comparison test (d) and one-way ANOVA with Tukey’s multiple-comparison test (e). Data are depicted as the mean ± s.e.m.
Source data
Role of CD4⁺ T cells and cDC1 cells in NK cell recruitment to tumours
a, Effect of CD4⁺ T cells on migratory DC populations in the tdLNs of mice immunized with MICB-vax versus Ctrl-vax. Total migratory DCs as well as cDC1 and cDC2 cells were quantified 2 d after induction of MICB expression in tumour cells by doxycycline treatment (n = 7 mice per group, except n = 6 for Ctrl-vax without anti-CD4). b, Migratory DC subsets within the tdLN of MICB-vax-immunized mice treated following immunization (days 28 + 30) with isotype-control, CD4-depleting or CD40L-blocking monoclonal antibody (n = 7 mice per group). c, Quantification of DC populations within the tumours of mice immunized with Ctrl-vax (blue) or MICB-vax (red) on day 7 following induction of MICB expression with doxycycline (n = 7 mice per group). d, Effect of cDC1 depletion on MICB vaccine-induced T cell and NK cell accumulation within tumours in Xcr1DTR mice. Mice were treated with DT or left untreated starting on day 26 following immunization with Ctrl-vax or MICB-vax (days 0 + 14) and B16F10 (MICB-dox) tumour implantation (day 21). Immune cells were analysed in tumours 7 d after induction of MICB expression on tumours with doxycycline (day 37) (n = 7 mice per group). e, Contribution of vaccine-induced anti-MICB antibodies to DC-mediated cross-presentation of tumour antigens to CD8⁺ T cells. Bone marrow-derived DCs (BMDCs) were pre-incubated with B2m-knockout B16F10 (MICB-OVA) tumour cells in the presence of affinity-purified serum IgG from mice immunized with Ctrl-vax or MICB-vax at the indicated concentrations. DCs were co-cultured with CFSE-labelled OT-1 CD8⁺ T cells with T cell proliferation as the readout. The role of activating Fc receptor (FcR) was assessed using BMDCs from Fcer1g–/– mice (orange) or pre-incubation of BMDCs with FcR-blocking antibody (yellow) before tumour cell addition. Representative data from two independent experiments are shown in a–e. Statistical significance was assessed by one-way ANOVA with Tukey’s multiple-comparison test (a, b, d), two-tailed Mann–Whitney test (c) and two-way ANOVA with Tukey’s multiple-comparison test (e). Data are depicted as the mean ± s.e.m. (a–d) or mean ± s.d. (e).
Source data
A vaccine targeting resistant tumours by dual T cell plus NK cell attack
  • Article
  • Publisher preview available

June 2022

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991 Reads

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101 Citations

Nature

Soumya Badrinath

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Maxence O. Dellacherie

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Aileen Li

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[...]

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Kai W. Wucherpfennig

Most cancer vaccines target peptide antigens, necessitating personalization owing to the vast inter-individual diversity in major histocompatibility complex (MHC) molecules that present peptides to T cells. Furthermore, tumours frequently escape T cell-mediated immunity through mechanisms that interfere with peptide presentation1. Here we report a cancer vaccine that induces a coordinated attack by diverse T cell and natural killer (NK) cell populations. The vaccine targets the MICA and MICB (MICA/B) stress proteins expressed by many human cancers as a result of DNA damage2. MICA/B serve as ligands for the activating NKG2D receptor on T cells and NK cells, but tumours evade immune recognition by proteolytic MICA/B cleavage3,4. Vaccine-induced antibodies increase the density of MICA/B proteins on the surface of tumour cells by inhibiting proteolytic shedding, enhance presentation of tumour antigens by dendritic cells to T cells and augment the cytotoxic function of NK cells. Notably, this vaccine maintains efficacy against MHC class I-deficient tumours resistant to cytotoxic T cells through the coordinated action of NK cells and CD4+ T cells. The vaccine is also efficacious in a clinically important setting: immunization following surgical removal of primary, highly metastatic tumours inhibits the later outgrowth of metastases. This vaccine design enables protective immunity even against tumours with common escape mutations. A vaccine targeting stress proteins expressed by many cancers blocks a tumour escape mechanism, enabling protective immunity mediated by diverse T cell and NK cell populations.

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Immunosuppressive Myeloid Cells Induce Nitric Oxide–Dependent DNA Damage and p53 Pathway Activation in CD8 + T Cells

January 2021

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44 Reads

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30 Citations

Cancer Immunology Research

Tumor-infiltrating myeloid-derived suppressor cells (MDSCs) are associated with poor survival outcomes in many human cancers. MDSCs inhibit T cell-mediated tumor immunity in part because they strongly inhibit T-cell function. However, whether MDSCs inhibit early or later steps of T-cell activation is not well established. Here we showed that MDSCs inhibited proliferation and induced apoptosis of CD8+ T cells even in the presence of dendritic cells (DCs) presenting a high-affinity cognate peptide. This inhibitory effect was also observed with delayed addition of MDSCs to co-cultures, consistent with functional data showing that T cells expressed multiple early activation markers even in the presence of MDSCs. Single-cell RNA-seq analysis of CD8+ T cells demonstrated a p53 transcriptional signature in CD8+ T cells co-cultured with MDSCs and DCs. Confocal microscopy showed induction of DNA damage and nuclear accumulation of activated p53 protein in a substantial fraction of these T cells. DNA damage in T cells was dependent on the iNOS enzyme and subsequent nitric oxide release by MDSCs. Small molecule-mediated inhibition of iNOS or inactivation of the Nos2 gene in MDSCs markedly diminished DNA damage in CD8+ T cells. DNA damage in CD8+ T cells was also observed in KPC pancreatic tumors but was reduced in tumors implanted into Nos2-deficient mice compared with wild-type mice. These data demonstrate that MDSCs do not block early steps of T-cell activation but rather induce DNA damage and p53 pathway activation in CD8+ T cells through an iNOS-dependent pathway.




PEI can be rapidly incorporated onto MSRs and leads to murine and human DC activation
a, Schematic representations of PEI and subsequent antigen adsorption onto bare MSRs. b, Incorporation efficiency of various doses of soluble B60K and L25K PEI into MSRs (n = 3). c, Incorporation kinetics of soluble B60K and L25K PEI into MSRs (representative data, repeated at least three times). d, Zeta potential of MSR–PEI particles using various doses of soluble B60K and L25K PEI (n = 3). e,f, Incorporation efficiency of murine (e) and human (f) neoantigen peptides (colour-codedaccording to the net charge at neutral pH) onto bare MSR or MSR–PEI particles using B60K PEI (n = 3, two-tailed t-test). g, Flow cytometry analysis of CD86 and MHC-II expression on murine BMDCs after 24 h of stimulation with 1 μg or 7 μg of soluble PEI or PBS (n = 4, compared with PBS by one-way analysis of variance (ANOVA)). h,i, Enzyme-linked immunosorbent assay (ELISA) analysis of TNF-α (h) and IL-6 (i) concentration in murine BMDC supernatant after 24 h of stimulation with 1 μg or 7 μg of soluble B60K and L25K PEI or PBS (n = 4, compared with PBS by one-way ANOVA). j, Flow cytometry analysis of SIINFEKL-presenting murine BMDCs after stimulation with PBS, OVA, and OVA with 5 μg or 10 μg of soluble B60K PEI (n = 3, compared with OVA by one-way ANOVA). Data depict mean ± s.d.
MSR–PEI vaccine enhances DC activation and trafficking in situ
a, Schematic representations of the MSR vaccine (V), boxed in black, and MSR–PEI vaccine (VP), boxed in red. b, Total cell number at the vaccine site explanted on day 3 after immunization with V or VP using B60K PEI (n = 4, two-tailed t-test). c–e, Total number of CD11c⁺ CD86⁺ activated DCs (n = 4, two-tailed t-test) (c), CD11c⁺ CCR7⁺ LN homing DCs (n = 4, two-tailed t-test) (d) and SIINFEKL-presenting DCs (n = 4, two-tailed t-test) (e) recruited to the vaccine site on day 3 after immunization with V or VP using B60K PEI. f–h, Total number of cells (n = 4 for day 3 and n = 5 for day 5, two-way ANOVA) (f), of CD11c⁺ CD86⁺ or CD11c⁺ MHC-II⁺ activated DCs (n = 4 for day 3 and n = 5 for day 5, two-way ANOVA) (g) and OVA⁺ DCs (n = 4 for day 3 and n = 5 for day 5, two-way ANOVA) (h) in the dLN on days 3 and 5 after immunization with V or VP using B60K PEI or left unimmunized (N). i, Schematic representations of the MSR–PEI trans vaccine (trans VP) and the MSR–PEI cis vaccine (cis VP). j, Total number of CD11c⁺ CD86⁺ activated DCs at the vaccine site on day 3 after immunization with the trans VP vaccine or the cis VP vaccine (n = 5, two-tailed t-test). k,l, Total number of CD11c⁺ CD86⁺ activated DCs (k) and CD11c⁺ OVA⁺ DCs (l) in the dLN on day 5 after immunization with the trans VP vaccine or the cis VP vaccine (n = 5, two-tailed t-test). Data depict mean ± s.d.
MSR–PEI vaccine enhances CD8 cytotoxic T-cell response against OVA
a, Percentage of IFN-γ⁺ CD8⁺ T cells isolated from peripheral blood on day 7 after immunization with V or VP using B60K PEI or left unimmunized, and stimulated with SIINFEKL (three primary fluorescence-activated cell sorting (FACS) plots on the left, quantifications from the FACS plots on the right) (n = 5, one-way ANOVA). b, Percentage of SIINFEKL-tetramer⁺ CD8⁺ T cells isolated from peripheral blood on day 7 after immunization with V or VP using B60K PEI or left unimmunized (N) (n = 5 for VP, n = 4 for N and V, one-way ANOVA). c, Ratio of CD8⁺ effector T cells (Teff) to CD4⁺ Foxp3⁺ regulatory T cells (Treg) at the MSR vaccine site on day 11 after immunization with V or VP using B60K PEI (n = 5, two-tailed t-test). d, Percentage of IFN-γ⁺ CD8⁺ T cells isolated from peripheral blood on day 7 after immunization with VP containing various doses of B60K PEI or left unimmunized (N) (n = 4, one-way ANOVA). e, Percentage of IFN-γ⁺ CD8⁺ T cells isolated from peripheral blood on day 7 after immunization with V or the MSR-PEI vaccine using L25K PEI (VP L25) or left unimmunized (N) (n = 4, one-way ANOVA). f, Percentage of IFN-γ⁺ CD8⁺ T cells isolated from peripheral blood on day 7 after immunization with V, the MSR-PEI trans vaccine (trans, VP) using B60K PEI or the MSR-PEI cis vaccine (cis, VP) using B60K PEI, or left unimmunized (N), and stimulated with SIINFEKL (n = 9, * between cis VP and trans VP, # between cis VP and V by one-way ANOVA). Data depict mean ± s.d.
MSR–PEI vaccine enhances CD8 cytotoxic T-cell response against E7 and regresses established tumours
a,b, Percentage of IFN-γ⁺ CD8⁺ T cells in response to RAHYNIVTF stimulation (a) and percentage of tetramer⁺ CD8⁺ T cells (b) in peripheral blood on day 7 after immunization with the MSR E7 vaccine (V) or the MSR–PEI E7 vaccine (VP) using 5 μg or 20 μg of B60K PEI, or left unimmunized (N) (n = 4, one-way ANOVA). c, ELISA analysis of TNF-α level in serum 24 h after vaccination with V or the MSR-PEI (B60K) vaccine (VP), or left unimmunized (N) (n = 4, compared with N by one-way ANOVA). d,e, Tumour growth (d) and overall survival (e) of mice bearing established E7-expressing TC-1 tumours (allowed to develop for 8 days) and treated with V or VP using L25K PEI, or left untreated (N), and subsequently rechallenged with TC-1 cells 6 months after the first inoculation (n = 10, compared with V by two-way ANOVA for d and by log-rank test for e). f, Overall survival of mice bearing established E7-expressing TC-1 tumours and treated with the MSR–PEI vaccine containing E7 (E7 VP) or the MSR–PEI vaccine containing SIINFEKL (SIINFEKL VP), or left untreated (Naive) (n = 8, compared with SIINFEKL VP by log-rank test). g, Flow cytometry analysis of blood T cells 3 days after treatment with a-CD8a monoclonal antibody (mab) or an isotype monoclonal antibody (representative data, repeated three times). h, Tumour growth of mice bearing established E7-expressing TC-1 tumours and treated with the MSR–PEI vaccine with either a-CD8a monoclonal antibody or an isotype monoclonal antibody (n = 8, compared with VP a-CD8 by two-way ANOVA). In a–c data depict mean ± s.d. and in d,h data depict mean ± s.e.m.
MSR–PEI vaccine enhances melanoma TIL effector function and induces tumour control and synergy with anti-CTLA4 therapy using combined B16 neoantigens
a, Number of CD44⁺ IFN-γ⁺, CD44⁺ TNF-α⁺ and CD44⁺ granzyme B⁺ TILs per 500,000 tumour cells on day 15 after inoculation. Mice bearing established B16F10 tumours (allowed to develop for 5 days) and treated with the MSR vaccine (V) or the MSR–PEI vaccine (VP) using L25K PEI and 50 μg of the B16 neoantigens, or left untreated (N) (n = 5 for VP, n = 3 for N and V, one-way ANOVA). b, Number of lung metastases formed on day 16 after inoculation in mice that received IV inoculation of B16F10 melanoma cells (allowed to develop for 1 day) and were treated with VP using L25K PEI and 50 μg of the B16 neoantigens, or left untreated (N). Primary representative photographs of excised lungs are shown (n = 6, two-tailed t-test). c, Tumour growth in mice bearing established B16F10 tumours (allowed to develop for 3 days) and treated with two injections of VP using L25K PEI and 50 μg of the B16 neoantigens on days 3 and 13, or left untreated (N) (n = 8, two-tailed t-test). d, Tumour volume change between days 13 and 17 after tumour inoculation (n = 8, two-tailed t-test). e, Tumour growth of mice bearing established B16F10 tumours (inoculated with 1 × 10⁵ cells) and treated with anti-CTLA4 antibody (a-CTLA4), anti-CTLA4 antibody in combination with the MSR–PEI vaccine (VP + a-CTLA4) using L25K PEI and 50 μg of the B16 neoantigens on day 5, or left untreated (N) (n = 8, *significant difference between VP + a-CTLA4 and a-CTLA4, ***significant difference between VP + a-CTLA4, ns between a-CTLA4 and N by one-way ANOVA). In a,b,d data depict mean ± s.d., in c,e data depict individual tumour growth.
A facile approach to enhance antigen response for personalized cancer vaccination

June 2018

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397 Reads

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358 Citations

Nature Materials

Existing strategies to enhance peptide immunogenicity for cancer vaccination generally require direct peptide alteration, which, beyond practical issues, may impact peptide presentation and result in vaccine variability. Here, we report a simple adsorption approach using polyethyleneimine (PEI) in a mesoporous silica microrod (MSR) vaccine to enhance antigen immunogenicity. The MSR-PEI vaccine significantly enhanced host dendritic cell activation and T-cell response over the existing MSR vaccine and bolus vaccine formulations. Impressively, a single injection of the MSR-PEI vaccine using an E7 peptide completely eradicated large, established TC-1 tumours in about 80% of mice and generated immunological memory. When immunized with a pool of B16F10 or CT26 neoantigens, the MSR-PEI vaccine eradicated established lung metastases, controlled tumour growth and synergized with anti-CTLA4 therapy. Our findings from three independent tumour models suggest that the MSR-PEI vaccine approach may serve as a facile and powerful multi-antigen platform to enable robust personalized cancer vaccination.


Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell–driven tumor immunity

March 2018

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431 Reads

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369 Citations

Science

Helping NK cells find their way MICA and MICB proteins can be expressed on tumors and act as “kill me” signals to the immune system. But tumors often disguise themselves by shedding these proteins, which prevents specialized natural killer (NK) cells from recognizing and destroying the cancer. Ferrari de Andrade et al. engineered antibodies directed against the site responsible for the proteolytic shedding of MICA and MICB (see the Perspective by Cerwenka and Lanier). The approach effectively locked MICA and MICB onto tumors so that NK cells could spot them for elimination. The antibodies exhibited preclinical efficacy in multiple tumor models, including humanized melanoma. Furthermore, the strategy reduced lung cancer metastasis after NK cell–mediated tumor lysis. Science , this issue p. 1537 ; see also p. 1460

Citations (4)


... Due to the lack of innate immunity, it is difficult to be recognized and killed by immune cells, and the immune checkpoint inhibitor ICIs are also difficult to play a role [1]. The cause of its immune deficiency may be (1) lack of tumor-related antigens (2) deficiency of antigen-presenting cells APCs (3) deletion of T cell activation (4) damage to the transport of T cells to the tumor [2]. Therefore, how to convert cold tumors into hot tumors is also a research hotspot in tumor treatment. ...

Reference:

The Role of Epidemic Tumor Vaccine in Cold Tumors to Hot Tumors
A vaccine targeting resistant tumours by dual T cell plus NK cell attack

Nature

... NO can directly induce T cell apoptosis by impairing the IL-2R signaling pathway, including the inhibition of Janus kinase (JAK)1 and JAK3, STAT5, extracellular signal-regulated kinase (Erk), and Akt phosphorylation (Mazzoni et al. 2002). Moreover, NO can induce DNA damage and activate the p53 pathway in CD8 + T cells, inducing T cell apoptosis (Cartwright et al. 2021). In conditions of low extracellular arginine, iNOS mediates the production of superoxide (O 2 − ), which reacts with other molecules to generate peroxynitrite (PNT) and reactive oxygen species (ROS) (Bronte and Zanovello 2005). ...

Immunosuppressive Myeloid Cells Induce Nitric Oxide–Dependent DNA Damage and p53 Pathway Activation in CD8 + T Cells
  • Citing Article
  • January 2021

Cancer Immunology Research

... 37 As a result, MICB is expressed by different types of human cancer. 38 In line with our results, ESCC tissues are characterized by the significant overexpression of MICB compared to its expression in adjacent normal tissues. 39 FAM189A2 is a unique activator of HECT-type ubiquitin E3 ligases that can regulate multiple aspects of cellular function by ubiquitinating various substrates. ...

Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell–driven tumor immunity
  • Citing Article
  • March 2018

Science

... [1,2] Welldesigned multifunctional nanovaccines can improve immune responses by enhancing various dimensions of immune activation pathways, such as boosting cellular uptake, [3,4] targeting antigen-presenting cells (APCs) or the lymphatic system, [3] or enhancing escape from endosomes. [5] However, current nanovaccine technologies rely on chemical or hybrid semibiological synthesis methods, [6,7] which significantly limit production efficiency. In contrast, engineered bacteria and mammalian cells can achieve complete protein biosynthesis. ...

A facile approach to enhance antigen response for personalized cancer vaccination

Nature Materials