Distinct immune signatures in directly treated and distant tumors result from TLR adjuvants and focal ablation

Theranostics
Michael ChavezKatherine W Ferrara

Abstract

Both adjuvants and focal ablation can alter the local innate immune system and trigger a highly effective systemic response. Our goal is to determine the impact of these treatments on directly treated and distant disease and the mechanisms for the enhanced response obtained by combinatorial treatments. Methods: We combined RNA-sequencing, flow cytometry and TCR-sequencing to dissect the impact of immunotherapy and of immunotherapy combined with ablation on local and systemic immune components. Results: With administration of a toll-like receptor agonist agonist (CpG) alone or CpG combined with same-site ablation, we found dramatic differences between the local and distant tumor environments, where the directly treated tumors were skewed to high expression of F4/80, Cd11b and Tnf and the distant tumors to enhanced Cd11c, Cd3 and Ifng. When ablation was added to immunotherapy, 100% (n=20/20) of directly treated tumors and 90% (n=18/20) of distant tumors were responsive. Comparing the combined ablation-immunotherapy treatment to immunotherapy alone, we find three major mechanistic differences. First, while ablation alone enhanced intratumoral antigen cross-presentation (up to ~8% of CD45+ cells), systemic cross-presentation of tum...Continue Reading

Citations

May 21, 2020·Proceedings of the National Academy of Sciences of the United States of America·Tali IlovitshKatherine W Ferrara
Aug 1, 2020·Frontiers in Immunology·Elke M MuntjewerffGeert van den Bogaart
Jan 30, 2019·Frontiers in Immunology·Tahir B DarStephen L Shiao
Oct 21, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jordan B JoinerPaul A Dayton
Jul 4, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jai Woong SeoKatherine W Ferrara
May 4, 2021·Frontiers in Immunology·Renske J E van den BijgaartGosse J Adema
Jun 3, 2021·Cancers·Ather AdnanRahul A Sheth
Jun 28, 2021·Drug Delivery and Translational Research·Samira Aghlara-FotovatOmid Veiseh
Jul 27, 2021·Frontiers in Oncology·Karl-Göran Tranberg
Aug 2, 2021·Advanced Drug Delivery Reviews·Nisi ZhangKatherine W Ferrara
Aug 6, 2021·Drug Delivery and Translational Research·Seung Woo ChungJung Soo Suk
Jul 31, 2021·Molecular Cancer Therapeutics·Alan P LombardAllen C Gao

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
transgenic
RNA-seq
flow
flow cytometry
RNAseq
ELISA
biopsies
Assay

Software Mentioned

Prism
GraphPad Prism
Adaptive
MATLAB
ImmunoSeq Analyzer
VDJTools
GraphPad
DAVID
ImmuneACCESS

Related Concepts

Related Feeds

Avian Influenza: Innate Immune Adjuvant (ASM)

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Avian Influenza: Innate Immune Adjuvant

Adjuvants systems that are added to vaccines against avian influenza have be explored to enhance the innate immune system response against the virus. Here is the latest research on avian influenza and the innate immune adjuvant.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.