Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site. VSports app下载.

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely V体育官网. .

Clinical Trial
. 2017 Nov 23;8(1):1738.
doi: 10.1038/s41467-017-01460-0.

Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma

Martin Lauss  1 , Marco Donia  2   3 , Katja Harbst  1 , Rikke Andersen  2   3 , Shamik Mitra  1 , Frida Rosengren  1 , Maryem Salim  1 , Johan Vallon-Christersson  1 , Therese Törngren  1 , Anders Kvist  1 , Markus Ringnér  4 , Inge Marie Svane  2   3 , Göran Jönsson  1
Affiliations
Clinical Trial

Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma

Martin Lauss et al. Nat Commun. .

Erratum in

Abstract

Adoptive T-cell therapy (ACT) is a highly intensive immunotherapy regime that has yielded remarkable response rates and many durable responses in clinical trials in melanoma; however, 50-60% of the patients have no clinical benefit. Here, we searched for predictive biomarkers to ACT in melanoma VSports手机版. Whole exome- and transcriptome sequencing and neoantigen prediction were applied to pre-treatment samples from 27 patients recruited to a clinical phase I/II trial of ACT in stage IV melanoma. All patients had previously progressed on other immunotherapies. We report that clinical benefit is associated with significantly higher predicted neoantigen load. High mutation and predicted neoantigen load are significantly associated with improved progression-free and overall survival. Further, clinical benefit is associated with the expression of immune activation signatures including a high MHC-I antigen processing and presentation score. These results improve our understanding of mechanisms behind clinical benefit of ACT in melanoma. .

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interests.

VSports注册入口 - Figures

Fig. 1
Fig. 1
Mutational load and clinical features of the cohort. Tumors are ordered according to mutational load and compared to clinical features. RECIST categories: CR complete response; PD progressive disease; PR partial response; SD\ stable disease
Fig. 2
Fig. 2
Mutational load is associated with benefit from ACT in melanoma. a Tumor mutational load by clinical response according to RECIST. P-value from Kruskal–Wallis test. Solid black line indicates the median. b Mutational load by clinical benefit groups, as defined in Methods section. P-value from Mann–Whitney test. c Tumor mutational load is significantly associated with progression-free survival, when the cohort in divided into three groups by mutational load. P-value from Cox regression. d Tumor mutational load is significantly associated with overall survival, when the cohort in divided into three groups by mutational load. P-value from Cox regression. RECIST categories: CR complete response; PD progressive disease; PR partial response; SD stable disease
Fig. 3
Fig. 3
Driver gene mutations and copy number aberrations are not associated with clinical benefit of ACT in melanoma a. Mutations in melanoma driver genes in tumors from patients without (left) and with (right) clinical benefit from ACT. There is no significant difference in mutation frequency between the groups in any of the genes, as shown on the right by the P-values from logistic regression with adjustment for mutational load of samples. b Fraction of exons with copy number changes for tumors from patients with and without clinical benefit. P-value from Mann–Whitney test. In this standard boxplot, the center line represents the median, the box limits represent the lower and upper quartiles, the whiskers extend to the most extreme values within 1.5xIQR. RECIST categories: CR complete response; PD progressive disease; PR partial response; SD stable disease
Fig. 4
Fig. 4
Expression of immune related genes and association to benefit from ACT in melanoma. a Enrichment plots from gene set enrichment analysis for the immune system and cell cycle pathways. b MHC class I expression score was constructed from indicated genes. c Progression-free and overall survival by MHC score quartile. P-values from Cox regression. d Expression of immune response related and melanoma lineage genes in patients with no clinical benefit (green) and with clinical benefit (orange). Signatures in the lower left panel (T and B cells, Macrophages, Endothelial cells, and CAF) are derived from publication by Tirosh et al.. Star denotes genes with significant association to benefit from ACT (P < 0.05, t-test)
Fig. 5
Fig. 5
Neoantigen load is associated with benefit from ACT in melanoma. a Expressed predicted neoantigens are depicted in patients with and without clinical benefit from ACT. b, c The number of expressed predicted neoantigens by RECIST response b and clinical benefit status c. P-value from Kruskal–Wallis and Mann–Whitney tests, respectively. Solid black line indicates the median. d Expressed predicted neoantigen load is significantly associated with progression-free (PFS) and overall survival (OS). P-value from Cox regression. RECIST categories: CR complete response, PD progressive disease, PR partial response, SD stable disease
See this image and copyright information in PMC

VSports在线直播 - References

    1. Svane IM, Verdegaal EM. Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma: what is needed to achieve standard of care? Cancer Immunol. Immunother. 2014;63:1081–1091. - VSports - PMC - PubMed
    1. Radvanyi LG, et al. Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clin. Cancer Res. 2012;18:6758–6770. - PMC - PubMed
    1. Rosenberg SA, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin. Cancer Res. 2011;17:4550–4557. - PMC (VSports在线直播) - PubMed
    1. Besser MJ, et al. Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: intent-to-treat analysis and efficacy after failure to prior immunotherapies. Clin. Cancer Res. 2013;19:4792–4800. - PubMed
    1. Besser MJ, et al. Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clin. Cancer Res. 2010;16:2646–2655. - PubMed

"V体育官网" Substances