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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5700 - Differential expression of PD-L1 and immune biomarkers by age: Decreased expression in pediatric/AYA patients with advanced cancer

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Omid Hamid

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

O. Hamid1, A.M. Vanderwalde2, C. Szeto3, S. Reddy3, S.K. Pal4

Author affiliations

  • 1 Research/immuno-oncology, The Angeles Clinic and Research Institute, 90025 - Los Angeles/US
  • 2 Hematology/oncology, University of Tennessee, 38104 - Memphis/US
  • 3 Bioinformatics, NantOmics, Culver City/US
  • 4 Medical Oncology And Therapeutics Research, City of Hope, 91010 - Duarte/US
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Resources

Abstract 5700

Background

The activity of immune checkpoint inhibitors (ICIs) varies substantially at the extremes of age. We interrogated our tissue database (n = 1,467) to determine if expression of checkpoint molecules or variations in tumor mutational burden (TMB) could explain this phenomenon.

Methods

Whole transcriptomic sequencing (RNA-Seq; ∼200x106 reads/tumor) was performed across 1,467 unselected clinical cases (NantHealth; Culver City, CA), with breast, colon, lung and sarcoma reflecting the most common tumor types assessed. To reflect the extremes of age, patients age < 25 and ≥ 80 were compared to the remainder of the cohort. PD-L1 expression was compared across these age-based subsets, along with CTLA4, TIGIT, FOXP3, LAG3, OX40, TIM3 and IDO expression. Putative markers of ICI resistance (e.g, VEGF-A/B/C) were also explored. Tumor mutational burden (TMB; defined as exonic nonsynonymous mutations/megabase [muts/Mb]) was characterized in each subset.

Results

Median age of the cohort was 59 (range, 2-97). Of 1,467 patients, 84 and 65 were age < 25 and ≥ 80, respectively. In patients < 25, significantly lower PD-L1, CTLA4, FOXP3, OX40, LAG3 and TIGIT levels were observed (P < 0.001 for each). No significant differences in IDO, LAG3 or TIM3 were observed in this younger cohort. Older patients had no significant differences in checkpoint molecule expression; curiously, a nonsignificant trend towards increased expression of PD-L1, FOXP3 and LAG3 was observed in the small subset of patients age ≥ 85. No differences in TMB were observed by age. Expression and TMB in each decile of age will be reported.

Conclusions

In pediatric and adolescent and young adult (AYA) patients, lower expression of multiple immune checkpoint molecules may have implications for immune combinatorial strategies. An opposing trend was seen in octagenarians and nonagenarians in our cohort. A detailed further breakdown by histologic subtype will be presented.

Clinical trial identification

Legal entity responsible for the study

Omid Hamid.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

O. Hamid: Consultant: Amgen, Novartis, Roche, BMS, Merck; Speaker: BMS, Genentech, Novartis, Amgen; Contracted research (for institution): AstraZeneca, BMS, Celldex, Genentech, Immunocore, Incyte, Merck, Merck-Serono, MedImmune, Novartis, Pfizer, Rinat, Roche. C. Szeto, S. Reddy: Employee and stockholder: NantOmics LLC. S.K. Pal: Consultant: Pfizer, Inc., Novartis, Aveo Pharmaceuticals, Inc., Myriad Genetics, Genentech, Inc., Exelixis, Bristol-Myers Squibb Company, Astellas Pharma, Inc.; Research/grant support: Medivation, Inc.; Honorarium: Novartis, Medivation, Inc., and Astellas Pharma, Inc. All other authors have declared no conflicts of interest.

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