Transcriptional Spatial Profiling of Cancer Tissues in the Era of Immunotherapy: The Potential and Promise DOI Open Access

Sanjna Nilesh Nerurkar,

Denise Goh, Chun Chau Lawrence Cheung

et al.

Cancers, Journal Year: 2020, Volume and Issue: 12(9), P. 2572 - 2572

Published: Sept. 9, 2020

Intratumoral heterogeneity poses a major challenge to making an accurate diagnosis and establishing personalized treatment strategies for cancer patients. Moreover, this might underlie resistance, disease progression, relapse. For example, while immunotherapies can confer high success rate, selective pressures coupled with dynamic evolution within tumour drive the emergence of drug-resistant clones that allow tumours persist in certain To improve immunotherapy efficacy, researchers have used transcriptional spatial profiling techniques identify subsequently block source heterogeneity. In review, we describe assess different technologies available such tissue. We first outline two well-known approaches, situ hybridization digital profiling. Then, highlight features emerging technology known as Visium Spatial Gene Expression Solution. generates quantitative gene expression data maps them tissue architecture. By retaining information, are well positioned novel biomarkers perform computational analyses inform on combinatorial immunotherapies.

Language: Английский

Redefining Tumor-Associated Macrophage Subpopulations and Functions in the Tumor Microenvironment DOI Creative Commons
Kaiyue Wu,

Kangjia Lin,

Xiaoyan Li

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 4, 2020

The immunosuppressive status of the tumour microenvironment (TME) remains poorly defined due to a lack understanding regarding function tumour-associated macrophages (TAMs), which are abundant in TME. TAMs crucial drivers progression, metastasis and resistance therapy. Intra- inter-tumoural spatial heterogeneities potential keys relationships between subpopulations their functions. Antitumour M1-like pro-tumour M2-like coexist within tumours, opposing effects these M1/M2 on tumours directly impact current strategies improve antitumour immune responses. Recent studies have found significant differences among monocytes or from distinct other investigations explored existence diverse TAM subsets at molecular level. In this review, we discuss emerging evidence highlighting redefinition functions TME possibility separating macrophage with into during development tumours. Such may relate differential cellular origin monocyte plasticity heterogeneity TAMs, all potentially biomarkers our how phenotypes dictated by ontogeny, activation localization. Therefore, detailed landscape must be deciphered integration new technologies, such as multiplexed immunohistochemistry (mIHC), mass cytometry time-of-flight (CyTOF), single-cell RNA-seq (scRNA-seq), transcriptomics systems biology approaches, for analyses

Language: Английский

Citations

531
Tumor Immunology and Tumor Evolution: Intertwined Histories DOI Creative Commons
Jérôme Galon, Daniela Bruni

Immunity, Journal Year: 2020, Volume and Issue: 52(1), P. 55 - 81

Published: Jan. 1, 2020

Language: Английский

Citations

462
Molecular testing and targeted therapy for non-small cell lung cancer: Current status and perspectives DOI
Evgeny N. Imyanitov, Aglaya G. Iyevleva, E. Levchenko

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2020, Volume and Issue: 157, P. 103194 - 103194

Published: Dec. 11, 2020

Language: Английский

Citations

384
Tumor-Infiltrating Lymphocytes and Their Prognostic Value in Cutaneous Melanoma DOI Creative Commons

Fabienne Maibach,

Hassan Sadozai, S. Morteza Seyed Jafari

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Sept. 10, 2020

Recent breakthroughs in tumor immunotherapy such as immune checkpoint blockade (ICB) antibodies, have demonstrated the capacity of system to fight cancer a number malignancies melanoma and lung cancer. The numbers, localization phenotypes tumor-infiltrating lymphocytes (TIL) are not only predictive response but also key modulators disease progression. In this review, we focus on TIL profiling cutaneous using histopathological approaches highlight observed prognostic value primary subsets. quantification formalin-fixed samples ranges from visual scoring lymphocytic infiltrates H&E multiplex immunohistochemistry immunofluorescence followed by enumeration image analysis software. Nevertheless, current literature primarily relies upon single marker analyses major lymphocyte subsets conventional T cells (CD3, CD4, CD8), regulatory (FOXP3) B (CD20). We review studies associations between patient survival. cover recent findings with respect existence ectopic lymphoid aggregates found TME which termed tertiary structures (TLS) generally positive feature. addition their significance, various sub-populations has been reported predict patient's ICB. Thus, potential patients receiving ICB discussed. Finally, describe recently developed state-of-the-art for infiltrating digital pathology algorithms (e.g. Immunoscore) proteomics-based immunophenotyping platforms imaging mass cytometry). Translating these novel technologies revolutionize immunopathology leading altering our understanding immunology dramatically improving outcomes patients.

Language: Английский

Citations

238
Tertiary lymphoid structures and B lymphocytes in cancer prognosis and response to immunotherapies DOI Creative Commons
Nicolas Jacquelot, Julie Tellier, Stephen L. Nutt

et al.

OncoImmunology, Journal Year: 2021, Volume and Issue: 10(1)

Published: Jan. 1, 2021

Tertiary lymphoid structures (TLS) are ectopic cellular aggregates that resemble secondary organs in their composition and structural organization. In contrast to organs, TLS not imprinted during embryogenesis but formed non-lymphoid tissues response local inflammation. exhibiting a variable degree of maturation found solid tumors. They composed various immune cell types including dendritic cells antigen-specific B T lymphocytes, together, actively drive the against tumor development progression. This review highlights successive steps leading formation its association with clinical outcomes. We discuss role played by tumor-infiltrating lymphocytes plasma cells, prognostic value tumors immunotherapeutic responses potential for future targeting.

Language: Английский

Citations

109
A robust multiplex immunofluorescence and digital pathology workflow for the characterisation of the tumour immune microenvironment DOI Creative Commons

Amélie Viratham Pulsawatdi,

Stephanie G. Craig, Victoria Bingham

et al.

Molecular Oncology, Journal Year: 2020, Volume and Issue: 14(10), P. 2384 - 2402

Published: July 16, 2020

Multiplex immunofluorescence is a powerful tool for the simultaneous detection of tissue-based biomarkers, revolutionising traditional immunohistochemistry. The Opal methodology allows up to eight biomarkers be measured concomitantly without cross-reactivity, permitting identification different cell populations within tumour microenvironment. In this study, we aimed validate multiplex workflow in two complementary panels and evaluate immune microenvironment colorectal cancer (CRC) formalin-fixed paraffin-embedded tissue. We stained CRC tonsil samples using on Leica BOND RX immunostainer. then acquired images an Akoya Vectra Polaris performed multispectral unmixing inform. Antibody were validated tissue microarray sections containing cores from six normal types, qupath image analysis. Comparisons between chromogenic immunohistochemistry consecutive same showed significant correlation (r

Language: Английский

Citations

95
The Cancer Immunotherapy Biomarker Testing Landscape DOI Open Access

Eric Walk,

Sophia Yohe, Amy Beckman

et al.

Archives of Pathology & Laboratory Medicine, Journal Year: 2019, Volume and Issue: 144(6), P. 706 - 724

Published: Nov. 12, 2019

Context.— Cancer immunotherapy provides unprecedented rates of durable clinical benefit to late-stage cancer patients across many tumor types, but there remains a critical need for biomarkers accurately predict response. Although some tests are associated with approved therapies and considered validated, other still emerging at various states translational exploration. Objective.— To provide pathologists current practical update on the evolving field testing. The scientific background, data, testing methodology following reviewed: programmed death ligand-1 (PD-L1), mismatch repair, microsatellite instability, mutational burden, polymerase δ ɛ mutations, neoantigens, tumor-infiltrating lymphocytes, transcriptional signatures immune responsiveness, resistance biomarkers, microbiome. Data Sources.— Selected publications trial data representing immunotherapy. Conclusions.— field, including use biomarker patient response, is in evolution. PD-L1, instability helping guide US Food Drug Administration–approved therapies, better predictors response resistance. Several categories characteristics underlying responsiveness may represent next generation predictive biomarkers. Pathologists have important roles responsibilities as continues develop, leadership studies, exploration novel accurate timely implementation newly validated companion diagnostics.

Language: Английский

Citations

83
Procedural Requirements and Recommendations for Multiplex Immunofluorescence Tyramide Signal Amplification Assays to Support Translational Oncology Studies DOI Open Access
Edwin R. Parra, Mei Jiang,

Luisa M. Solis

et al.

Cancers, Journal Year: 2020, Volume and Issue: 12(2), P. 255 - 255

Published: Jan. 21, 2020

In the development of a multiplex immunofluorescence (IF) platform and optimization validation new IF panels using tyramide signal amplification system, several technical requirements are important for high-quality staining, analysis, results. The aim this review is to discuss basic performing (TSA) in formalin-fixed, paraffin-embedded cancer tissues support translational oncology research. Our laboratory has stained approximately 4000 tumor samples TSA system immune profiling labeled biomarkers single slide elucidate biology at protein level identify therapeutic targets biomarkers. By analyzing proteins thousands cells on slide, technique provides systems-level view various processes tissues. Although technology shows high flexibility studies, it presents challenges when applied study different histology cancers. experience that adequate antibody validation, staining optimization, analysis strategies, data generation steps generating quality Tissue management, fixation procedures, storage, cutting can also affect results assay must be standardized. Overall, method reliable supporting research given precise, step-by-step approach.

Language: Английский

Citations

83
Predictors of Response, Progression-Free Survival, and Overall Survival in Patients With Lung Cancer Treated With Immune Checkpoint Inhibitors DOI Creative Commons
Regan M. Memmott, Adam R. Wolfe, David P. Carbone

et al.

Journal of Thoracic Oncology, Journal Year: 2021, Volume and Issue: 16(7), P. 1086 - 1098

Published: April 9, 2021

Language: Английский

Citations

80
Multiplexed ion beam imaging (MIBI) for characterization of the tumor microenvironment across tumor types DOI Creative Commons

Jason Ptacek,

Darren Locke,

Rachel Finck

et al.

Laboratory Investigation, Journal Year: 2020, Volume and Issue: 100(8), P. 1111 - 1123

Published: March 23, 2020

Language: Английский

Citations

75