Immuno-genomic characterisation of high-grade serous ovarian cancer reveals immune evasion mechanisms and identifies an immunological subtype with a favourable prognosis and improved therapeutic efficacy

Sun, Jie; Yan, Congcong; Xu, Dandan; Zhang, Zicheng; Li, Ké; Li, Xiaobo; Zhou, Meng; Hao, Dapeng

doi:10.1038/s41416-021-01692-4

Cited by 23 publications

(25 citation statements)

References 40 publications

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“…In this study, we set out to comprehensively examine immunotranscriptomic and immune infiltrate changes resulting from NACT exposure in a large cohort of HGSOC patients. Our findings are mostly consistent with previous studies examining smaller cohorts of matched pre- and post-NACT tumors that reported increases in immune cell infiltration and upregulation of specific immunoreactive genes ( 30 , 31 ). Our data revealed that in addition to the regulation of genes known for mediating cytotoxic effects of chemotherapy, chemotherapy exposure was also accompanied by an upregulation of genes that could impede its efficacy and/or promote chemoresistance.…”

Section: Discussionsupporting

confidence: 92%

“…In addition to specific gene and pathway changes, we also observed significant increases in immune infiltration following NACT, which is well corroborated by previous studies ( 16 , 17 , 19 , 20 , 31 , 50 ). Furthermore, we validated the finding at the protein level that CD8+ T cells were significantly increased in post-NACT tumors.…”

Section: Discussionsupporting

confidence: 91%

“…For example, Sun et al. observed enrichment of specific subsets of immune cells and greater cytolytic activity in patients with chemosensitive disease when analyzing publicly available datasets ( 31 ). Likewise, Hao et al.…”

Section: Discussionmentioning

confidence: 99%

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Adaptive transcriptomic and immune infiltrate responses in the tumor immune microenvironment following neoadjuvant chemotherapy in high grade serous ovarian cancer reveal novel prognostic associations and activation of pro-tumorigenic pathways

et al. 2022

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The high rate of ovarian cancer recurrence and chemoresistance necessitates further research into how chemotherapy affects the tumor immune microenvironment (TIME). While studies have shown that immune infiltrate increases following neoadjuvant (NACT) chemotherapy, there lacks a comprehensive understanding of chemotherapy-induced effects on immunotranscriptomics and cancer-related pathways and their relationship with immune infiltrate and patient responses. In this study, we performed NanoString nCounter® PanCancer IO360 analysis of 31 high grade serous ovarian cancer (HGSOC) patients with matched pre-treatment biopsy and post-NACT tumor. We observed increases in pro-tumorigenic and immunoregulatory pathways and immune infiltrate following NACT, with striking increases in a cohort of genes centered on the transcription factors ATF3 and EGR1. Using quantitative PCR, we analyzed several of the top upregulated genes in HGSOC cell lines, noting that two of them, ATF3 and AREG, were consistently upregulated with chemotherapy exposure and significantly increased in platinum resistant cells compared to their sensitive counterparts. Furthermore, we observed that pre-NACT immune infiltrate and pathway scores were not strikingly related to platinum free interval (PFI), but post-NACT immune infiltrate, pathway scores, and gene expression were. Finally, we found that higher levels of a cohort of proliferative and DNA damage-related genes was related to shorter PFI. This study underscores the complex alterations in the ovarian TIME following chemotherapy exposure and begins to untangle how immunologic factors are involved in mediating chemotherapy response, which will allow for the future development of novel immunologic therapies to combat chemoresistance.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

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Adaptive transcriptomic and immune infiltrate responses in the tumor immune microenvironment following neoadjuvant chemotherapy in high grade serous ovarian cancer reveal novel prognostic associations and activation of pro-tumorigenic pathways

et al. 2022

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“…In addition, genetic variants may be closely related to tumor heterogeneity, which is a natural consequence of genome mutations ( Vitale et al, 2021 ). Tumor heterogeneity can affect the development and progression of cancer by forcing cancer cells into the tumor microenvironment (TME), enabling tumor cells to evade recognition and elimination by the immune system, and thus, it is a critical factor influencing clinical prognosis and response to immunotherapy in GC ( Zhang et al, 2021 ; Sun et al, 2022 ). Therefore, future studies will need to characterize the geographic distribution of genetic variants of GC samples to understand their contribution to GC development.…”

Section: Introductionmentioning

confidence: 99%

Multidimensional difference analysis in gastric cancer patients between high and low latitude

et al. 2022

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Genetic variation has been shown to affect tumor growth and progression, and the temperature at different latitudes may promote the evolution of genetic variation. Geographical data with latitudinal information is of importance to understand the interplay between genetic variants and environmental influence, such as the temperature, in gastric cancer (GC). In this study, we classified the GC samples from The Cancer Genome Atlas database into two groups based on the latitudinal information of patients and found that GC samples with low-latitude had better clinical outcomes. Further analyses revealed significant differences in other clinical factors such as disease stage and grade between high and low latitudes GC samples. Then, we analyzed the genomic and transcriptomic differences between the two groups. Furthermore, we evaluated the activity score of metabolic pathways and infiltrating immune cells in GC samples with different latitudes using the single-sample gene set enrichment analysis algorithm. These results showed that GC samples at low-latitude had lower tumor mutation burden and subclones as well as higher DNA repair activities. Meanwhile, we found that most immune cells were associated with the prognosis of low-latitude GC patients. At last, we constructed and validated an immune-related prognostic model to evaluate the prognosis of GC samples at different latitudes. This study has provided a further understanding of the geographical contribution to GC at the multiomic level and may benefit the individualized treatment of GC patients at different latitudes.

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“…Substantial evidence suggests that tumor heterogeneity increases the likelihood that cancer cells survive conventional chemotherapy and targeted anticancer drugs ( 8 – 10 ). In addition, tumor heterogeneity affects the efficacy of immunotherapies, especially immune checkpoint inhibitors ( 11 – 13 ). However, the exploration of molecular mechanism underlying the histologic heterogeneity remained nascent ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional patterns reveal tumor histologic heterogeneity and immunotherapy response in lung adenocarcinoma

Jiao¹,

Liu²,

Liu³

2022

Front. Immunol.

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Tumoral heterogeneity has proven to be a leading cause of difference in prognosis and acquired drug resistance. High intratumor heterogeneity often means poor clinical response and prognosis. Histopathological subtypes suggest tumor heterogeneity evolved during the progression of lung adenocarcinoma, but the exploration of its molecular mechanisms remains limited. In this work, we first verified that transcriptional patterns of a set of differentially expressed genes profoundly revealed the histologic progression of lung adenocarcinoma. Next, a predictive model based on the transcriptional patterns was established to accurately distinguish histologic subtypes. Two crucial genes were identified and used to construct a tumor heterogeneous scoring model (L2SITH) to stratify patients, and we found that patients with low heterogeneity score had better prognosis. Low L2SITH scores implied low tumor purity and beneficial tumor microenvironment. Moreover, L2SITH effectively identified cohorts with better responses to anti–PD-1 immunotherapy.

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Immuno-genomic characterisation of high-grade serous ovarian cancer reveals immune evasion mechanisms and identifies an immunological subtype with a favourable prognosis and improved therapeutic efficacy

Cited by 23 publications

References 40 publications

Adaptive transcriptomic and immune infiltrate responses in the tumor immune microenvironment following neoadjuvant chemotherapy in high grade serous ovarian cancer reveal novel prognostic associations and activation of pro-tumorigenic pathways

Adaptive transcriptomic and immune infiltrate responses in the tumor immune microenvironment following neoadjuvant chemotherapy in high grade serous ovarian cancer reveal novel prognostic associations and activation of pro-tumorigenic pathways

Multidimensional difference analysis in gastric cancer patients between high and low latitude

Transcriptional patterns reveal tumor histologic heterogeneity and immunotherapy response in lung adenocarcinoma

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