Comprehensive Genomic Profiling of Rare Tumors in China: Routes to Immunotherapy

Abstract

Treatment options for rare tumors are limited, and comprehensive genomic profiling may provide useful information for novel treatment strategies and improving outcomes. The aim of this study is to explore the treatment opportunities of patients with rare tumors using immune checkpoint inhibitors (ICIs) that have already been approved for routine treatment of common tumors. We collected immunotherapy-related indicators data from a total of 852 rare tumor patients from across China, including 136 programmed cell death ligand-1 (PD-L1) expression, 821 tumors mutational burden (TMB), 705 microsatellite instability (MSI) and 355 human leukocyte antigen class I (HLA-I) heterozygosity reports. We calculated the positive rates of these indicators and analyzed the consistency relationship between TMB and PD-L1, TMB and MSI, and HLA-I and PD-L1. The prevalence of PD-L1 positive, TMB-H, MSI-, and HLA-I -heterozygous was 47.8%, 15.5%, 7.4%, and 78.9%, respectively. The consistency ratio of TMB and PD-L1, TMB and MSI, and HLA-I and PD-L1 was 54.8% (78/135), 87.3% (598/685), and 47.4% (54/114), respectively. The prevalence of the four indicators varied widely across tumors systems and subtypes. The probability that neuroendocrine tumors (NETs) and biliary tumors may benefit from immunotherapy is high, since the proportion of TMB-H is as high as 50% and 25.4% respectively. The rates of PD-L1 positivity, TMB-H and MSI-H in carcinoma of unknown primary (CUP) were relatively high, while the rates of TMB-H and MSI-H in soft tissue tumors were both relatively low. Our study revealed the distribution of immunotherapeutic indicators in patients with rare tumors in China. Comprehensive genomic profiling may offer novel therapeutic modalities for patients with rare tumors to solve the dilemma of limited treatment options.

KRAS Mutation in Rare Tumors: A Landscape Analysis of 3453 Chinese Patients

“…All samples were tested by NGS in the Geneplus-Beijing laboratory, which is accredited by American College of Pathologists ( Sun et al, 2019 ; Wang et al, 2020 ; Zhuo et al, 2020 ; Wang et al, 2021 ). Briefly, all tissue samples were hematoxylin-eosin stained and reviewed to ensure a minimum of 20% tumor cells.…”

“…Our team has previously studied the genomic profiling of rare tumors in China, which indicated that employing targeted therapy and immunotherapy in rare tumors is highly feasible ( Wang et al, 2020 ; Wang et al, 2021 ). However, the molecular landscape of KRAS mutation in rare tumors has not been studied.…”

Uncovering the flip side of immune checkpoint inhibitors: a comprehensive review of immune-related adverse events and predictive biomarkers

“…In a cross-sectional study involving 54 cancer patients undergoing anti-PD-1 or anti-PD-L1 therapy and 50 healthy controls, there was a statistically significant rise in APA observed among these patients 126 . Furthermore, the impact of the host's germline on the response to ICI therapy is worth exploring, and human leukocyte antigen class I (HLA-I) serves as a valuable prognostic biomarker for this purpose 127 . CD8 + T cells play a major role in the antitumor activity of ICIs and are required to present tumor antigens via HLA-I 128 .…”

Targeting rare tumors: new focus for clinical research in China

“…In recent decades, great progress has been made in immunotherapy for advanced cancer leading to a substantial survival benefit in multiple solid tumors, including gastric, liver, NSCLC, etc. We investigated the expression levels of programmed cell death ligand-1 (PD-L1) in 852 rare tumor patients, finding a prevalence of 47.8% positivity, which is higher than the prevalence found in common cancers with approved indications for immunotherapy (Wang et al, 2021). Both MSI and TMB are recognized predictive biomarkers for response to immune checkpoint inhibitors by the FDA in multiple solid tumors.…”