Emphasizing the comparison between biofloc and semi-floc systems with respect to productivity and immune responses of Penaeus vannamei (Boone, 1931)

Towards addressing questions related to HIV pathogenesis and vaccine design we are fortunate to have the availability of the SIV-infected rhesus macaque model. The strengths of this model which include a rapid rate of progression to AIDS and knowledge of the dose route and strain of the infecting virus complement studies in HIV-infected patients in which the reagents host genetics and access to samples are more extensive and better defined. Unfortunately there is currently still too little known about the antiviral immune responses in either system to directly and accurately compare their similarities and differences and to draw any definitive conclusions. Therefore the data and views presented herein will simply reflect what has recently been discovered in both humans and non-human primate studies. (excerpt)

Genetically Programmed Biases in Th1 and Th2 Immune Responses Modulate Atherogenesis

Immunomodulation in the critically ill

Genome-wide transcriptome analysis of hippocampus in rats indicated that TLR/NLR signaling pathway was involved in the pathogenisis of depressive disorder induced by chronic restraint stress.

Gene replacement therapies, like organ and cell transplantation, are likely to introduce neoantigens that elicit rejection via humoral and/or effector T-cell immune responses. Nonetheless, thanks to an ever-growing body of preclinical studies; it is now well accepted that gene transfer protocols can be specifically designed and optimized for induction of antigen-specific immune tolerance. One approach is to specifically express a gene in a tissue with a tolerogenic microenvironment such as the liver or thymus. Another strategy is to transfer a particular gene into hematopoietic stem cells or immunological precursor cells thus educating the immune system to recognize the therapeutic protein as “self.” In addition, expression of the therapeutic protein in protolerogenic antigen-presenting cells such as immature dendritic cells and B cells has proven to be promising. All three approaches have successfully prevented unwanted immune responses in preclinical studies aimed at the treatment of inherited protein deficiencies, e.g., lysosomal storage disorders and hemophilia, and of type 1 diabetes and multiple sclerosis. In this review, we focus on current gene transfer protocols that induce tolerance, including gene delivery vehicles and target tissues, and discuss successes and obstacles in different disease models.

Identifying New Immune Response Dynamics in Virus-Associated Cancers

Replication stress is a common feature of solid cancers, and drugs targeting replication stress such as Checkpoint kinase 1 inhibitors (CHK1i) have demonstrated significant preclinical activity especially in combination with replication stress promoting chemotherapies. However, this has not translated into an effective clinical treatment, primarily due to high normal tissue toxicity. We have previously demonstrated that a combination of CHK1i with a subclinical dose of hydroxyurea selectively targets a range of tumour types, importantly with little normal tissue toxicity to even chemo-sensitive tissues. The CHK1i combination also promotes a pro-inflammatory response and immunogenic cell death. In vivo, this drug combination induces tumour regression which is dependent on an adaptive immune response. Here we report the immune responses triggered by this combination in mouse models and demonstrate that this response is suppressed by tumour-associated myeloid cells. Syngeneic mouse melanoma and ovarian cancer models were treated in vivo with the combination of CHK1i SRA737 and low dose hydroxyurea. The tumour immune microenvironment and peripheral immune cell responses were assessed by single cell expression analysis and immune cell marker multiparameter flow cytometry. In the panel of cancer models tested in syngeneic mice, the CHK1i combination, controlled tumour growth. Immune responses were elicited by the CHK1i combination in all tumours but found different types of immune cell responses in the different models and cancers investigated. The combination enhanced immune responses independent of the initial tumour immune microenvironment, including in tumours that were immunologically “cold”. The common features of the immune responses in all the models are increased cytolytic activity and reduced immune suppression in the tumour microenvironment. The responses were dependent on CD8+ T cells. Myeloid cells in the tumour microenvironment were immunosuppressive, expressing high levels of PD-L1 in response to treatment. This could be reduced by depletion with CSF-1R antibody or reducing tumour CSF-1 expression. This demonstrates the CHK1i combination is highly selective with minimal normal tissue toxicity, does not adversely affect immune responses, and can trigger an effective anti-tumour immune response in range of tumour settings, including current treatment resistant tumours. Reducing tumour associated myeloid number or activity was associated with enhanced anti-tumour immune responses. This work suggests that the myeloid component of tumours may significantly alter treatment responses by suppressing anti-tumour immune activity and that targeting this population may enhance the durability of the anti-tumour immune response even in immunologically cold tumours. Citation Format: Zhen Zeng, Ritu Bhatt, Anastasia Gandini, Jazmina Gonzalez Cruz, Martina Proctor, Katharine Irvine, Riccardo Dolcetti, James Wells, Brian Gabrielli. Targeting Replication Stress Promotes Anti-tumour Immune Responses that are Suppressed by Tumour-associated Myeloid cells [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A118.

Immunology

Mitochondria are multifaceted organelles representing the "powerhouse of cells" for their function as bioenergetics and biosynthetic hubs. In addition, they play an essential role in the regulation of innate and adaptive immune responses, including host defenses against viruses, as well as in inflammatory responses 1 . This peculiar role of mitochondria is principally due to the activation of adaptor mitochondrial proteins, known as mitochondrial antiviral signaling (MAVS) proteins. MAVS sense viral RNA and trigger the activation of the transcription factor NF-kB or IFN pathways and autophagy, in order to clear the infection and avoid excessive inflammation, respectively1 .

Purpose: Vaccination with HER2 peptide-pulsed DC1s stimulates a HER2-specific T-cell response. This randomized trial aimed to establish safety and evaluate immune and clinical responses to vaccination via intralesional (IL), intranodal (IN), or both intralesional and intranodal (ILN) injection.Experimental Design: Fifty-four HER2pos patients [42 pure ductal carcinoma in situ (DCIS), 12 early invasive breast cancer (IBC)] were enrolled in a neoadjuvant HER2 peptide-pulsed DC1 vaccine trial. Patients were randomized to IL (n = 19), IN (n = 19), or ILN (n = 16) injection. Immune responses were measured in peripheral blood and sentinel lymph nodes by ELISPOT or in vitro sensitization assay. Pathologic response was assessed in resected surgical specimens.Results: Vaccination by all injection routes was well tolerated. There was no significant difference in immune response rates by vaccination route (IL 84.2% vs. IN 89.5% vs. ILN 66.7%; P = 0.30). The pathologic complete response (pCR) rate was higher in DCIS patients compared with IBC patients (28.6% vs. 8.3%). DCIS patients who achieved pCR (n = 12) and who did not achieve pCR (n = 30) had similar peripheral blood anti-HER2 immune responses. All patients who achieved pCR had an anti-HER2 CD4 immune response in the sentinel lymph node, and the quantified response was higher by response repertoire (P = 0.03) and cumulative response (P = 0.04).Conclusions: Anti-HER2 DC1 vaccination is a safe and immunogenic treatment to induce tumor-specific T-cell responses in HER2pos patients; immune and clinical responses were similar independent of vaccination route. The immune response in the sentinel lymph nodes, rather than in the peripheral blood, may serve as an endpoint more reflective of antitumor activity. Clin Cancer Res; 23(12); 2961-71. ©2016 AACR.

Innate Immune Dysfunction in Trauma Patients

SARS-CoV-2 antibody response eight months after vaccination with mRNA vaccines. Influence of prior SARS-CoV-2 exposure

Adaptive immune cell responses as therapeutic targets in antibody-mediated organ rejection.

Integrating microRNAs into a system biology approach to acute lung injury

<div>Abstract<p><b>Purpose:</b> Vaccination with HER2 peptide-pulsed DC1s stimulates a HER2-specific T-cell response. This randomized trial aimed to establish safety and evaluate immune and clinical responses to vaccination via intralesional (IL), intranodal (IN), or both intralesional and intranodal (ILN) injection.</p><p><b>Experimental Design:</b> Fifty-four HER2<sup>pos</sup> patients [42 pure ductal carcinoma <i>in situ</i> (DCIS), 12 early invasive breast cancer (IBC)] were enrolled in a neoadjuvant HER2 peptide-pulsed DC1 vaccine trial. Patients were randomized to IL (<i>n</i> = 19), IN (<i>n</i> = 19), or ILN (<i>n</i> = 16) injection. Immune responses were measured in peripheral blood and sentinel lymph nodes by ELISPOT or <i>in vitro</i> sensitization assay. Pathologic response was assessed in resected surgical specimens.</p><p><b>Results:</b> Vaccination by all injection routes was well tolerated. There was no significant difference in immune response rates by vaccination route (IL 84.2% vs. IN 89.5% vs. ILN 66.7%; <i>P</i> = 0.30). The pathologic complete response (pCR) rate was higher in DCIS patients compared with IBC patients (28.6% vs. 8.3%). DCIS patients who achieved pCR (<i>n</i> = 12) and who did not achieve pCR (<i>n</i> = 30) had similar peripheral blood anti-HER2 immune responses. All patients who achieved pCR had an anti-HER2 CD4 immune response in the sentinel lymph node, and the quantified response was higher by response repertoire (<i>P</i> = 0.03) and cumulative response (<i>P</i> = 0.04).</p><p><b>Conclusions:</b> Anti-HER2 DC1 vaccination is a safe and immunogenic treatment to induce tumor-specific T-cell responses in HER2<sup>pos</sup> patients; immune and clinical responses were similar independent of vaccination route. The immune response in the sentinel lymph nodes, rather than in the peripheral blood, may serve as an endpoint more reflective of antitumor activity. <i>Clin Cancer Res; 23(12); 2961–71. ©2016 AACR</i>.</p></div>