Memory CD8+ T cell responses to cancer

Han, Jichang; Khatwani, Nikhil; Searles, Tyler G.; Turk, Mary Jo; Angeles, Christina V.

doi:10.1016/j.smim.2020.101435

Cited by 93 publications

(85 citation statements)

References 138 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We noted the expansion at 22 days of an expanded population of CD62L+CD44+ CD8+ T cells, suggesting the development of central memory T cells in the tumor. This T cell memory subset has been noted in mice and humans to be important for both clearance of tumors and prevention of their recurrence 17 . As before, the proportion of Tregs was markedly reduced in the primary tumor.…”

Section: Resultsmentioning

confidence: 99%

Global anti-tumor immunity after localized, bioengineered Treg depletion

Majedi

Hasani-Sadrabadi

Thauland

et al. 2021

Preprint

View full text Add to dashboard Cite

Over 90% of deaths from cancer occur due to solid tumors, occurring at a rate of ~1,500 deaths per day in the US, highlighting a profound and unmet need for new therapies. Solid tumors evade clearance by T cells due to a variety of immunosuppressive properties of the tumor microenvironment. However, this immunosuppression cannot be easily blocked on a global level because systemic activation of the immune system elicits a host of complications. An ideal therapy for solid tumors would act locally to activate the immune response without evoking global adverse effects. Here we present a biodegradable, macroporous scaffold that is implanted adjacent to the tumor and suppresses the main obstacle to cancer immunosurveillance: intratumoral regulatory T cells. The scaffold also promotes the recruitment and activation of T cell effectors into the tumor, resulting in clearance of otherwise aggressive and fatal tumors in mice. Unexpectedly, the local depletion of Tregs results in an "immunological abscopal effect" acting on distant tumors. We demonstrate that this versatile platform can also deliver tumor-antigen-specific T cells directly to the peri-tumoral environment, bypassing difficulties in intravenous delivery including the environmental barriers imposed by the tumor's vasculature. By orchestrating multiple local immunomodulatory treatments, this scaffold offers a general approach to engineer T-cell responses to solid tumors without systemic toxicities.

show abstract

Section: Resultsmentioning

confidence: 99%

Global anti-tumor immunity after localized, bioengineered Treg depletion

Majedi

Hasani-Sadrabadi

Thauland

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Additionally, some new immunotherapies, such as adoptive cell therapy ( 75 ), oncolytic virus therapy ( 76 ), and tumor vaccines ( 77 ) can be used to change the TIME. Their effects were examined in combination with IC inhibitors in HIS mouse models.…”

Section: Therapeutic Strategies For Different Tumor Types In His Micementioning

confidence: 99%

Strategies for the Construction of Mouse Models With Humanized Immune System and Evaluation of Tumor Immune Checkpoint Inhibitor Therapy

et al. 2021

View full text Add to dashboard Cite

Immunotherapy has been used as a first-line treatment for a variety of advanced tumors, allowing remarkable progress to be made in cancer treatment. Nonetheless, only a small number of patients can benefit from immune checkpoint inhibitor monotherapy. To improve the effect of immunotherapy, the underlying mechanism of combination therapy was investigated in the context of an intact human tumor immune microenvironment using mice with a human immune system (HIS) bearing human tumors. Herein, we summarize and discuss strategies for the development and use of HIS mice models in tumor immunotherapies. Most importantly, this review proposes a method of t11umor identification and classification in HIS mice based on the tumor-infiltrating lymphocytes and PD-L1 expression, and according to this classification, we propose different combination treatment strategies that can be utilized to enhance the effect of immunotherapy. Thus, we provide effective experimental schemes for tumor immunotherapy in HIS mice models.

show abstract

“…In addition, immune cell infiltration has downstream functions in oncogenic pathways, and the microenvironment has a close relationship with responses to immunotherapies [ 17 ]. CD8+ T cells are known to be effective regulators of adaptive immunity for eliminating both pathogen-infected cells and tumour cells [ 18 ] and play an important role in tumour immunity [ 19 ]. M2-type macrophages are known to be crucial regulators in the tumour microenvironment through their inhibitory activity [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions

et al. 2021

View full text Add to dashboard Cite

Background Hepatocellular carcinoma (HCC) has a poor prognosis and has become the sixth most common malignancy worldwide due to its high incidence. Advanced approaches to therapy, including immunotherapeutic strategies, have played crucial roles in decreasing recurrence rates and improving clinical outcomes. The HCC microenvironment is important for both tumour carcinogenesis and immunogenicity, but a classification system based on immune signatures has not yet been comprehensively described. Methods HCC datasets from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and the International Cancer Genome Consortium (ICGC) were used in this study. Gene set enrichment analysis (GSEA) and the ConsensusClusterPlus algorithm were used for clustering assessments. We scored immune cell infiltration and used linear discriminant analysis (LDA) to improve HCC classification accuracy. Pearson's correlation analyses were performed to assess relationships between immune signature indices and immunotherapies. In addition, weighted gene co-expression network analysis (WGCNA) was applied to identify candidate modules closely associated with immune signature indices. Results Based on 152 immune signatures from HCC samples, we identified four distinct immune subtypes (IS1, IS2, IS3, and IS4). Subtypes IS1 and IS4 had more favourable prognoses than subtypes IS2 and IS3. These four subtypes also had different immune system characteristics. The IS1 subtype had the highest scores for IFNγ, cytolysis, angiogenesis, and immune cell infiltration among all subtypes. We also identified 11 potential genes, namely, TSPAN15, TSPO, METTL9, CD276, TP53I11, SPINT1, TSPO, TRABD2B, WARS2, C9ORF116, and LBH, that may represent potential immunological biomarkers for HCC. Furthermore, real-time PCR revealed that SPINT1, CD276, TSPO, TSPAN15, METTL9, and WARS2 expression was increased in HCC cells. Conclusions The present gene-based immune signature classification and indexing may provide novel perspectives for both HCC immunotherapy management and prognosis prediction.

show abstract

Memory CD8+ T cell responses to cancer

Cited by 93 publications

References 138 publications

Global anti-tumor immunity after localized, bioengineered Treg depletion

Global anti-tumor immunity after localized, bioengineered Treg depletion

Strategies for the Construction of Mouse Models With Humanized Immune System and Evaluation of Tumor Immune Checkpoint Inhibitor Therapy

Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions

Contact Info

Product

Resources

About