Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions

Rita T Lawlor; Paola Mattiolo; Andrea Mafficini; Seung-Mo Hong; Maria L Piredda; Sergio V Taormina; Giuseppe Malleo; Giovanni Marchegiani; Antonio Pea; Roberto Salvia; Valentyna Kryklyva; Jae Il Shin; Lodewijk A Brosens; Michele Milella; Aldo Scarpa; Claudio Luchini

doi:10.3390/cancers13133119

Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions

Rita T Lawlor, Paola Mattiolo, Andrea Mafficini, Seung-Mo Hong, Maria L Piredda, Sergio V Taormina, Giuseppe Malleo, Giovanni Marchegiani, Antonio Pea, Roberto Salvia, Valentyna Kryklyva, Jae Il Shin, Lodewijk A Brosens, Michele Milella, Aldo Scarpa, Claudio Luchini

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Abstract

Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to immunotherapy. In this systematic review, we assessed the potential predictive role of high-TMB in pancreatic ductal adenocarcinoma (PDAC), as well as the histo-molecular features of high-TMB PDAC. High-TMB appeared as a rare but not-negligible molecular feature in PDAC, being present in about 1.1% of cases. This genetic condition was closely associated with mucinous/colloid and medullary histology (p < 0.01). PDAC with high-TMB frequently harbored other actionable alterations, with microsatellite instability/defective mismatch repair as the most common. Immunotherapy has shown promising results in high-TMB PDAC, but the sample size of high-TMB PDAC treated so far is quite small. This study highlights interesting peculiarities of PDAC harboring high-TMB and may represent a reliable starting point for the assessment of TMB in the clinical management of patients affected by pancreatic cancer.

Original language	English
Article number	3119
Pages (from-to)	1-15
Journal	Cancers
Volume	13
Issue number	13
DOIs	https://doi.org/10.3390/cancers13133119
Publication status	Published - 22 Jun 2021

Keywords

PD-1
PD-L1
TMB
TML
immunotherapy
pancreatic cancer
tumor mutation burden

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Lawlor, R. T., Mattiolo, P., Mafficini, A., Hong, S.-M., Piredda, M. L., Taormina, S. V., Malleo, G., Marchegiani, G., Pea, A., Salvia, R., Kryklyva, V., Shin, J. I., Brosens, L. A., Milella, M., Scarpa, A., & Luchini, C. (2021). Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions. Cancers, 13(13), 1-15. Article 3119. https://doi.org/10.3390/cancers13133119

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title = "Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions",

abstract = "Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to immunotherapy. In this systematic review, we assessed the potential predictive role of high-TMB in pancreatic ductal adenocarcinoma (PDAC), as well as the histo-molecular features of high-TMB PDAC. High-TMB appeared as a rare but not-negligible molecular feature in PDAC, being present in about 1.1% of cases. This genetic condition was closely associated with mucinous/colloid and medullary histology (p < 0.01). PDAC with high-TMB frequently harbored other actionable alterations, with microsatellite instability/defective mismatch repair as the most common. Immunotherapy has shown promising results in high-TMB PDAC, but the sample size of high-TMB PDAC treated so far is quite small. This study highlights interesting peculiarities of PDAC harboring high-TMB and may represent a reliable starting point for the assessment of TMB in the clinical management of patients affected by pancreatic cancer.",

keywords = "PD-1, PD-L1, TMB, TML, immunotherapy, pancreatic cancer, tumor mutation burden",

author = "Lawlor, {Rita T} and Paola Mattiolo and Andrea Mafficini and Seung-Mo Hong and Piredda, {Maria L} and Taormina, {Sergio V} and Giuseppe Malleo and Giovanni Marchegiani and Antonio Pea and Roberto Salvia and Valentyna Kryklyva and Shin, {Jae Il} and Brosens, {Lodewijk A} and Michele Milella and Aldo Scarpa and Claudio Luchini",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = jun,

day = "22",

doi = "10.3390/cancers13133119",

language = "English",

volume = "13",

pages = "1--15",

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Lawlor, RT, Mattiolo, P, Mafficini, A, Hong, S-M, Piredda, ML, Taormina, SV, Malleo, G, Marchegiani, G, Pea, A, Salvia, R, Kryklyva, V, Shin, JI, Brosens, LA, Milella, M, Scarpa, A & Luchini, C 2021, 'Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions', Cancers, vol. 13, no. 13, 3119, pp. 1-15. https://doi.org/10.3390/cancers13133119

TY - JOUR

T1 - Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer

T2 - Systematic Review and Still-Open Questions

AU - Lawlor, Rita T

AU - Mattiolo, Paola

AU - Mafficini, Andrea

AU - Hong, Seung-Mo

AU - Piredda, Maria L

AU - Taormina, Sergio V

AU - Malleo, Giuseppe

AU - Marchegiani, Giovanni

AU - Pea, Antonio

AU - Salvia, Roberto

AU - Kryklyva, Valentyna

AU - Shin, Jae Il

AU - Brosens, Lodewijk A

AU - Milella, Michele

AU - Scarpa, Aldo

AU - Luchini, Claudio

PY - 2021/6/22

Y1 - 2021/6/22

N2 - Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to immunotherapy. In this systematic review, we assessed the potential predictive role of high-TMB in pancreatic ductal adenocarcinoma (PDAC), as well as the histo-molecular features of high-TMB PDAC. High-TMB appeared as a rare but not-negligible molecular feature in PDAC, being present in about 1.1% of cases. This genetic condition was closely associated with mucinous/colloid and medullary histology (p < 0.01). PDAC with high-TMB frequently harbored other actionable alterations, with microsatellite instability/defective mismatch repair as the most common. Immunotherapy has shown promising results in high-TMB PDAC, but the sample size of high-TMB PDAC treated so far is quite small. This study highlights interesting peculiarities of PDAC harboring high-TMB and may represent a reliable starting point for the assessment of TMB in the clinical management of patients affected by pancreatic cancer.

AB - Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to immunotherapy. In this systematic review, we assessed the potential predictive role of high-TMB in pancreatic ductal adenocarcinoma (PDAC), as well as the histo-molecular features of high-TMB PDAC. High-TMB appeared as a rare but not-negligible molecular feature in PDAC, being present in about 1.1% of cases. This genetic condition was closely associated with mucinous/colloid and medullary histology (p < 0.01). PDAC with high-TMB frequently harbored other actionable alterations, with microsatellite instability/defective mismatch repair as the most common. Immunotherapy has shown promising results in high-TMB PDAC, but the sample size of high-TMB PDAC treated so far is quite small. This study highlights interesting peculiarities of PDAC harboring high-TMB and may represent a reliable starting point for the assessment of TMB in the clinical management of patients affected by pancreatic cancer.

KW - PD-1

KW - PD-L1

KW - TMB

KW - TML

KW - immunotherapy

KW - pancreatic cancer

KW - tumor mutation burden

U2 - 10.3390/cancers13133119

DO - 10.3390/cancers13133119

M3 - Review article

C2 - 34206554

SN - 2072-6694

VL - 13

SP - 1

EP - 15

JO - Cancers

JF - Cancers

IS - 13

M1 - 3119

ER -

Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions

Abstract

Keywords

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