scholarly journals Immune Responses Raised in an Experimental Colon Carcinoma Model Following Oral Administration of Lactobacillus casei

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 368 ◽  
Author(s):  
Georgios Aindelis ◽  
Angeliki Tiptiri-Kourpeti ◽  
Evangeli Lampri ◽  
Katerina Spyridopoulou ◽  
Eleftheria Lamprianidou ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Oral Administration ◽  
Tumor Growth ◽  
Colon Carcinoma ◽  
Lactobacillus Casei ◽  
Tumor Tissue ◽  
Cell Infiltration ◽  
T Cell Infiltration ◽  
Anti Cancer

The role of dietary probiotic strains on host anti-cancer immune responses against experimental colon carcinoma was investigated. We have previously shown that Lactobacillus casei administration led to tumor growth suppression in an experimental colon cancer model. Here, we investigated the underlying immune mechanisms involved in this tumor-growth inhibitory effect. BALB/c mice received daily live lactobacilli per os prior to the establishment of a syngeneic subcutaneous CT26 tumor. Tumor volume, cytokine production, T cell differentiation and migration, as well as tumor cell apoptosis were examined to outline potential immunomodulatory effects following L. casei oral intake. Probiotic administration in mice resulted in a significant increase in interferon gamma (IFN-γ), Granzyme B and chemokine production in the tumor tissue as well as enhanced CD8+ T cell infiltration, accompanied by a suppression of tumor growth. Cytotoxic activity against cancer cells was enhanced in probiotic-fed compared to control mice, as evidenced by the elevation of apoptotic markers, such as cleaved caspase 3 and poly (ADP-ribose) polymerase 1 (PARP1), in tumor tissue. Oral administration of Lactobacillus casei induced potent Th1 immune responses and cytotoxic T cell infiltration in the tumor tissue of tumor-bearing mice, resulting in tumor growth inhibition. Thus, the microorganism may hold promise as a novel dietary immunoadjuvant in raising protective anti-cancer immune responses.

scholarly journals Salmonella Breaks Tumor Immune Tolerance by Downregulating Tumor Programmed Death-Ligand 1 Expression

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 57
Author(s):  
Man-Chin Chen ◽  
Christian Ronquillo Pangilinan ◽  
Che-Hsin Lee
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Immune Checkpoint ◽  
Immune Escape ◽  
Cell Infiltration ◽  
Tumor Immune Escape ◽  
Programmed Death Ligand 1 ◽  
T Cell Infiltration ◽  
Programmed Death

Immunotherapy is becoming a popular treatment modality in combat against cancer, one of the world’s leading health problems. While tumor cells influence host immunity via expressing immune inhibitory signaling proteins, some bacteria possess immunomodulatory activities that counter the symptoms of tumors. The accumulation of Salmonella in tumor sites influences tumor protein expression, resulting in T cell infiltration. However, the molecular mechanism by which Salmonella activates T cells remains elusive. Many tumors have been reported to have high expressions of programmed death-ligand 1 (PD-L1), which is an important immune checkpoint molecule involved in tumor immune escape. In this study, Salmonella reduced the expression of PD-L1 in tumor cells. The expression levels of phospho-protein kinase B (P-AKT), phospho-mammalian targets of rapamycin (P-mTOR), and the phospho-p70 ribosomal s6 kinase (P-p70s6K) pathway were revealed to be involved in the Salmonella-mediated downregulation of PD-L1. In a tumor-T cell coculture system, Salmonella increased T cell number and reduced T cell apoptosis. Systemic administration of Salmonella reduced the expressions of PD-L-1 in tumor-bearing mice. In addition, tumor growth was significantly inhibited along with an enhanced T cell infiltration following Salmonella treatment. These findings suggest that Salmonella acts upon the immune checkpoint, primarily PD-L1, to incapacitate protumor effects and thereby inhibit tumor growth.

scholarly journals Rapid Copper Acquisition by Developing Murine Mesothelioma: Decreasing Bioavailable Copper Slows Tumor Growth, Normalizes Vessels and Promotes T Cell Infiltration

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e73684 ◽  
Author(s):  
Andrew Crowe ◽  
Connie Jackaman ◽  
Katie M. Beddoes ◽  
Belinda Ricciardo ◽  
Delia J. Nelson
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Cell Infiltration ◽  
T Cell Infiltration

scholarly journals Therapeutic Induction of Tertiary Lymphoid Structures in Cancer Through Stromal Remodeling

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna Johansson-Percival ◽  
Ruth Ganss
Keyword(s):  
T Cell ◽  
Tumor Microenvironment ◽  
Cancer Immunotherapy ◽  
Tumor Rejection ◽  
Cell Infiltration ◽  
Cytotoxic T Cell ◽  
T Cell Infiltration ◽  
Anti Cancer ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

Improving the effectiveness of anti-cancer immunotherapy remains a major clinical challenge. Cytotoxic T cell infiltration is crucial for immune-mediated tumor rejection, however, the suppressive tumor microenvironment impedes their recruitment, activation, maturation and function. Nevertheless, solid tumors can harbor specialized lymph node vasculature and immune cell clusters that are organized into tertiary lymphoid structures (TLS). These TLS support naïve T cell infiltration and intratumoral priming. In many human cancers, their presence is a positive prognostic factor, and importantly, predictive for responsiveness to immune checkpoint blockade. Thus, therapeutic induction of TLS is an attractive concept to boost anti-cancer immunotherapy. However, our understanding of how cancer-associated TLS could be initiated is rudimentary. Exciting new reagents which induce TLS in preclinical cancer models provide mechanistic insights into the exquisite stromal orchestration of TLS formation, a process often associated with a more functional or “normalized” tumor vasculature and fueled by LIGHT/LTα/LTβ, TNFα and CC/CXC chemokine signaling. These emerging insights provide innovative opportunities to induce and shape TLS in the tumor microenvironment to improve immunotherapies.

scholarly journals Arf1-mediated lipid metabolism sustains cancer cells and its ablation induces anti-tumor immune responses in mice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Guohao Wang ◽  
Junji Xu ◽  
Jiangsha Zhao ◽  
Weiqin Yin ◽  
Dayong Liu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
T Cell ◽  
Immune Responses ◽  
Cancer Cells ◽  
Immune Surveillance ◽  
Therapeutic Vaccine ◽  
Treatment Resistance ◽  
Inverse Correlation ◽  
Cell Infiltration ◽  
T Cell Infiltration

AbstractCancer stem cells (CSCs) may be responsible for treatment resistance, tumor metastasis, and disease recurrence. Here we demonstrate that the Arf1-mediated lipid metabolism sustains cells enriched with CSCs and its ablation induces anti-tumor immune responses in mice. Notably, Arf1 ablation in cancer cells induces mitochondrial defects, endoplasmic-reticulum stress, and the release of damage-associated molecular patterns (DAMPs), which recruit and activate dendritic cells (DCs) at tumor sites. The activated immune system finally elicits antitumor immune surveillance by stimulating T-cell infiltration and activation. Furthermore, TCGA data analysis shows an inverse correlation between Arf1 expression and T-cell infiltration and activation along with patient survival in various human cancers. Our results reveal that Arf1-pathway knockdown not only kills CSCs but also elicits a tumor-specific immune response that converts dying CSCs into a therapeutic vaccine, leading to durable benefits.

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