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Comment
. 2021 Jan 15;27(2):380-382.
doi: 10.1158/1078-0432.CCR-20-3877. Epub 2020 Nov 16.

CDK12 Deficiency and the Immune Microenvironment in Prostate Cancer

Tamara L Lotan  1   2   3 , Emmanuel S Antonarakis  2   3
Affiliations
Comment

CDK12 Deficiency and the Immune Microenvironment in Prostate Cancer

Tamara L Lotan et al. Clin Cancer Res. .

Abstract

CDK12 inactivation in prostate cancer is associated with tandem genomic duplications that may generate fusion-associated neoantigens and elicit immune responses amenable to checkpoint blockade. In the first study to comprehensively characterize the T-cell immune microenvironment of CDK12-deficient prostate cancers, subsets of immunosuppressive CD4+FOXP3- T cells were increased compared with CDK12-proficient controls.See related article by Rescigno et al., p. 566.

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Conflict of interest statement

Disclosure/Conflict of Interest: TLL has received research support from Roche/Ventana Medical Systems and DeepBio for other studies. ESA has served as a paid consultant/advisor for Janssen, Pfizer, Sanofi, Dendreon, Merck, Bristol-Myers Squibb, AstraZeneca, Clovis, Eli Lilly and Amgen; has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Merck, Bristol-Myers Squibb, AstraZeneca and Constellation; and is a co-inventor of an AR-V7 biomarker technology that has been licensed to Qiagen.

Figures

Figure.
Figure.
Putative mechanisms of sensitivity or resistance to PD-1 inhibitor therapy or PARP inhibitor therapy among CDK12-deficient prostate cancer patients. Understanding the potential genomic, transcriptomic and immune microenvironment differences in CDK12-altered prostate cancers may help to guide treatment decisions for this subset of patients.
See this image and copyright information in PMC

Comment in

  • Characterizing CDK12-Mutated Prostate Cancers.
    Rescigno P, Gurel B, Pereira R, Crespo M, Rekowski J, Rediti M, Barrero M, Mateo J, Bianchini D, Messina C, Fenor de la Maza MD, Chandran K, Carmichael J, Guo C, Paschalis A, Sharp A, Seed G, Figueiredo I, Lambros M, Miranda S, Ferreira A, Bertan C, Riisnaes R, Porta N, Yuan W, Carreira S, de Bono JS. Rescigno P, et al. Clin Cancer Res. 2021 Jan 15;27(2):566-574. doi: 10.1158/1078-0432.CCR-20-2371. Epub 2020 Sep 28. Clin Cancer Res. 2021. PMID: 32988971 Free PMC article.

Comment on

  • Characterizing CDK12-Mutated Prostate Cancers.
    Rescigno P, Gurel B, Pereira R, Crespo M, Rekowski J, Rediti M, Barrero M, Mateo J, Bianchini D, Messina C, Fenor de la Maza MD, Chandran K, Carmichael J, Guo C, Paschalis A, Sharp A, Seed G, Figueiredo I, Lambros M, Miranda S, Ferreira A, Bertan C, Riisnaes R, Porta N, Yuan W, Carreira S, de Bono JS. Rescigno P, et al. Clin Cancer Res. 2021 Jan 15;27(2):566-574. doi: 10.1158/1078-0432.CCR-20-2371. Epub 2020 Sep 28. Clin Cancer Res. 2021. PMID: 32988971 Free PMC article.

References

    1. Rescigno P, Gurel B, Pereira R, Crespo M, Rekowski J, Rediti M, et al. Characterizing CDK12-mutated prostate cancers. Clin Cancer Res. 2020. - PMC - PubMed
    1. Bajrami I, Frankum JR, Konde A, et al. Genome-wide profiling of genetic synthetic lethality identifies CDK12 as a novel determinant of PARP1/2 inhibitor sensitivity. Cancer Res. 2014;74:287–97. - PMC - PubMed
    1. Quigley DA, Dang HX, Zhao SG, Lloyd P, Aggarwal R, Alumkal JJ, et al. Genomic hallmarks and structural variation in metastatic prostate cancer. Cell 2018;174:758–69 e9. - PMC - PubMed
    1. Antonarakis ES, Isaacsson Velho P, Fu W, Wang H, Agarwal N, Sacristan Santos V, et al. CDK12-altered prostate cancer: Clinical features and therapeutic outcomes to standard systemic therapies, poly (ADP-ribose) polymerase inhibitors, and PD-1 inhibitors. JCO Precis Oncol. 2020;4:370–81. - PMC - PubMed
    1. Guedes LB, Antonarakis ES, Schweizer MT, Mirkheshti N, Almutairi F, Park JC, et al. MSH2 loss in primary prostate cancer. Clin Cancer Res. 2017;23:6863–74. - PMC - PubMed

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