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. 2021 Mar 15;3(1):vdab045.
doi: 10.1093/noajnl/vdab045. eCollection 2021 Jan-Dec.

Disappearance of MMR-deficient subclones after controlled IL-12 and PD-1 inhibition in a glioma patient

Matthew McCord  1 , Rimas V Lukas  2 , Christina Amidei  3 , Nathan Demars  4 , Arnold Gelb  5 , Jill Buck  4 , Sean Sachdev  6 , Alexander Feldman  1 , Matthew Tate  3 , Karan Dixit  2 , Daniel J Brat  1 , Lawrence Jennings  1 , Craig Horbinski  1   3
Affiliations

Disappearance of MMR-deficient subclones after controlled IL-12 and PD-1 inhibition in a glioma patient

Matthew McCord et al. Neurooncol Adv. .
No abstract available

Keywords: DNA mismatch repair; IDH; glioma; immunotherapy.

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Figures

Figure 1.
Figure 1.
Histologic features of glioma, pre- and post-combination immunotherapy. Hypermutated glioma prior to immunotherapy: (A) hypercellular neoplasm with palisading necrosis. (B) Many cells showed extreme nuclear atypia. (C) Markedly atypical mitoses were also present. Recurrent glioma post-immunotherapy: (D) The majority of resected tissue showed features consistent with a recurrent tumor, including palisading necrosis. (E) Nuclear atypia was present but was not as severe as in the pre-immunotherapy sample, and atypical mitoses were not identified. (F) Approximately 20–30% of the resected tumor showed therapy-related necrosis and granulomas (arrowheads). (G) Granulomas were non-caseating, with numerous multinucleated giant cells (arrowheads), positive for CD68 and CD163 (not shown). (H and I) Accompanying the granulomas was a brisk mixed inflammatory infiltrate containing numerous plasma cells (I, arrowheads) and eosinophils (I, arrows). Length of scale bar in (I) is equivalent to 100 μm in (A), (D), and (F), 40 μm in (G), 20 μm in (B), (E), and (H), and 10 μm in (C).
Figure 2.
Figure 2.
Postmortem findings. (A) Postmortem examination of the original tumor resection cavity showed abundant viable tumor cells, including markedly atypical cells, as was seen prior to immunotherapy. Granulomas, eosinophils, and plasma cells were no longer present anywhere in the brain. Tumor spread diffusely throughout all brain regions sampled, including the midbrain (B, asterisk = central aqueduct), cerebellum (C, asterisk = granular neurons, arrows = tumor cells), pons (D), and medulla (E, asterisk = fourth ventricle). Leptomeningeal dissemination was present, all the way down into the spinal cord, around the nerve rootlets in the thoracic region (F, arrow = tumor, asterisk = nerve rootlet). Scale bar in (F) = 80 μm in (A), 400 μm in (B), 200 μm in (C–F).
See this image and copyright information in PMC

References

    1. Chiocca EA, Yu JS, Lukas RV, et al. . Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: results of a phase 1 trial. Sci Transl Med. 2019;11(505). - PMC - PubMed
    1. Cloughesy TF, Mochizuki AY, Orpilla JR, et al. . Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med. 2019;25(3):477–486. - PMC - PubMed
    1. Schalper KA, Rodriguez-Ruiz ME, Diez-Valle R, et al. . Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma. Nat Med. 2019;25(3):470–476. - PubMed
    1. Rizvi NA, Hellmann MD, Snyder A, et al. . Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–128. - PMC - PubMed
    1. Lukas RV, Rodon J, Becker K, et al. . Clinical activity and safety of atezolizumab in patients with recurrent glioblastoma. J Neurooncol. 2018;140(2):317–328. - PubMed

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