Immune profiling of pediatric solid tumors

Abstract

Pediatric cancers, particularly high-risk solid tumors, urgently need effective and specific therapies. Their outlook has not appreciably improved in decades. Immunotherapies such as immune checkpoint inhibitors offer much promise, but most are only approved for use in adults. Though several hundred clinical trials have tested immune-based approaches in childhood cancers, few have been guided by biomarkers or clinical-grade assays developed to predict patient response and, ultimately, to help select those most likely to benefit. There is extensive evidence in adults to show that immune profiling has substantial predictive value, but few studies focus on childhood tumors, because of the relatively small disease population and restricted use of immune-based therapies. For instance, only one published study has retrospectively examined the immune profiles of pediatric brain tumors after immunotherapy. Furthermore, application and integration of advanced multiplex techniques has been extremely limited. Here, we review the current status of immune profiling of pediatric solid tumors, with emphasis on tumor types that represent enormous unmet clinical need, primarily in the context of immune checkpoint inhibitor therapy. Translating optimized and informative immune profiling into standard practice and access to personalized combination therapy will be critical if childhood cancers are to be treated effectively and affordably.

Figure 1. Techniques used for immunoprofiling.

IHC, immunohistochemistry; mIHC, multiplex IHC; RNA-Seq, RNA sequencing; TCR-Seq, T cell receptor sequencing.

Figure 2. Multiplex IHC in melanoma using two different antibody panels to immunoclassify solid tumors.

(A and B) Immuno-infiltrated tumors. (C and D) Immuno-altered tumors. A and C include CD4⁺, CD8⁺, FoxP3⁺CD4⁺ Treg, SOX10⁺, PD-L1, and DAPI. B and D include CD3⁺, CD20⁺, CD11c⁺, PD-L1⁺, SOX10⁺, CD68⁺, and DAPI. Original magnification of OPAL images, ×200.

Figure 3. New approach using immune context classification of tumors to guide anticancer therapy and increase the response to immune checkpoint inhibitors.

ADORA2A, A_2a adenosine receptor; CSF1R, colony-stimulating factor 1 receptor; DDR, DNA damage response; HDAC, histone deacetylase; IDO, indoleamine 2,3-dioxygenase; LIGHT, tumor necrosis factor superfamily member 14; STING, stimulator of IFN genes.