Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors

Yi, Ming; Jiao, Dechao; Xu, Hanxiao; Liu, Qian; Zhao, Wei; Han, Xinwei; Wu, Kongming

doi:10.1186/s12943-018-0864-3

Cited by 615 publications

(515 citation statements)

References 136 publications

(135 reference statements)

Supporting

Mentioning

458

Contrasting

Unclassified

Order By: Relevance

“…Additional immune‐oncology markers such as high TMB are under investigation as part of late phase clinical trials . However, it remains to be seen whether immune checkpoint inhibitors will have efficacy for the treatment of EMPD.…”

Section: Discussionmentioning

confidence: 99%

“…6 Additional immune-oncology markers such as high TMB are under investigation as part of late phase clinical trials. 38,39 However, it remains to be seen whether immune checkpoint inhibitors will have efficacy for the treatment of EMPD. We observed some patients with high TMB and the presence of PD-L1 in IC (TIL) in our study of EMPD, indicating that these F I G U R E 3 The same case provided in Figure 2 with a PD-L1 positivity in the inflammatory (immune cells, IC; upper right image, white arrow); Please note the absence of PD-L1 expression in tumor cells (TC; white arrow); Lower two images show HER2 (left) and TOP2A gene co-amplifications (right image) (Chromogenic in situ hybridization).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

et al. 2020

View full text Add to dashboard Cite

Background Primary Extra‐mammary Paget's disease (EMPD) is a very rare cutaneous adenocarcinoma affecting anogenital or axillary regions. It is characterized by a prolonged course with recurrences and eventually distant metastatic spread for which no specific therapy is known. Methods Eighteen EMPD (13 vulvar and five scrotal) and ten mammary Paget's disease (MPD) cases were comprehensively profiled for gene mutations, fusions and copy number alterations, and for therapy‐relevant protein biomarkers). Results Mutations in TP53 and PIK3CA were the most frequent in both cohorts: 7/15 and 5/15 in EMPD; 1/6 and 4/7 in MPD HER2 gene amplification was detected in 4/18 EMPD (3 vulvar and 1 scrotal case) in contrast to MPD where it was detected in the majority (7/8) of cases. TOP2A gene amplification was seen in 2/12 EMPD and 1/6 MPD, respectively. Similarly, no difference in estrogen receptor expression was seen between the EMPD (4/15) and MPD (3/10). Androgen receptor was also expressed in the majority of both cohorts (12/16 EMPD) and (7/8 MPD).Here ARv7 splice variant was detected in 1/7 EMPD and 1/4 MPD cases, respectively. PD‐L1 expression on immune cells was exclusively observed in three vulvar EMPD. In contrast to MPD, six EMPDs harbored a “high” tumor mutation burden (≥10 mutations/Mb). All tested cases from both cohorts were MSI stable. Conclusions EMPD shares some targetable biomarkers with its mammary counterpart (steroid receptors, PIK3CA signaling pathways, TOP2A amplification). HER2 positivity is notably lower in EMPD while biomarkers to immune checkpoint inhibitors (high TMB and PD‐L1) were observed in some EMPD. Given that no consistent molecular alteration characterizes EMPD, comprehensive theranostic profiling is required to identify individual patients with targetable molecular alterations.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

et al. 2020

View full text Add to dashboard Cite

show abstract

“…It has been demonstrated that AYA with fusion-positive sarcomas have poorer prognosis compared with younger patients, but to our knowledge there is no comparison with OA in the literature. 11 Extensive genomic characterization has been made of adult STS, 12 but there certainly is a great need for further biological and translocational studies to demonstrate possible differences between AYA and other age groups with the same STS subtype. 5 Factors influencing the possible sensitivity to immunotherapy, such as copy number load, PD-L1 expression, infiltrating T cells, and microsatellite instability, also need to be investigated further.…”

Section: Discussionmentioning

confidence: 99%

“…5 Factors influencing the possible sensitivity to immunotherapy, such as copy number load, PD-L1 expression, infiltrating T cells, and microsatellite instability, also need to be investigated further. 11 Extensive genomic characterization has been made of adult STS, 12 but there certainly is a great need for further biological and translocational studies to demonstrate possible differences between AYA and other age groups with the same STS subtype. Such information could be valuable for interventional studies comparing the efficacy of treatment in AYA compared with OA.…”

Section: Discussionmentioning

confidence: 99%

Soft‐tissue sarcoma in adolescents and young adults compared with older adults: A report among 5000 patients from the Scandinavian Sarcoma Group Central Register

Papworth

Arroyo

Styring

et al. 2019

Cancer

View full text Add to dashboard Cite

BACKGROUND: In recent years, there has been growing awareness of the distinct characteristics of adolescents and young adults (AYA) diagnosed with cancer. Soft-tissue sarcoma (STS) accounts for approximately 1% of all cancers diagnosed in adults and 8% of cancers diagnosed in AYA. To the best of our knowledge, only a few sarcoma registers include data regarding histological subtype, age at diagnosis, and detailed clinical information. Therefore, little is known regarding clinical presentation and outcomes in AYA diagnosed with STS. METHODS: Using the Scandinavian Sarcoma Group Central Register, data were obtained regarding 4977 patients who were diagnosed with STS for the period between 1986 and 2011. AYA (those aged 18-39 years) were compared with older adults (OA; those aged 40-80 years) with respect to clinical presentation, treatment, and outcome. RESULTS: There were 868 AYA and 4109 OA. Overall and by STS subtype, there were significant differences noted between AYA and OA with regard to presentation, treatment, and survival. The distribution of STS subtypes was different between OA and AYA (eg, OA were more likely to be diagnosed with malignant fibrous histiocytoma compared with AYA [34% vs 16%; P < .001]). OA also were more likely to have tumors measuring ≥5 cm (68% vs 56%; P < .001) and a higher malignancy grade (75% vs 67%; P < .001). In the majority of STS subtypes AYA had significantly better overall survival and less disease recurrence compared with OA, but this finding was not true for those with malignant peripheral nerve sheath tumors. CONCLUSIONS: There are several differences between AYA and OA with STS with regard to presentation, treatment, and survival, and such differences must be taken into consideration when designing clinical trials. Additional work also is needed to characterize the potential biological mechanisms underlying these differences. Cancer 2019;125:3595-3602.

show abstract

“…Mechanistically, checkpoint inhibition, and IL-10 treatment together enhances the number and quality of pre-existing TILs. The efficacy of PD-1/PD-L1 inhibitors is highly associated with tumor microenvironment such as TIL density, PD-1/PD-L1 expression; tumor intrinsic feature, such as tumor mutational burden, microsatellite instability; as well as gut microbiota (62). The clinical trials of pegylated recombinant human IL-10 are focused on several solid tumor types.…”

Section: Il-10 Functions As An Immune Activating Cytokine In Cancer Imentioning

confidence: 99%

The Complement Receptors C3aR and C5aR Are a New Class of Immune Checkpoint Receptor in Cancer Immunotherapy

Wang

Zhang

2019

Front. Immunol.

View full text Add to dashboard Cite

Cancer immunotherapy has made remarkable clinical advances in recent years. Antibodies targeting the immune checkpoint receptors PD-1 and CTLA-4 and adoptive cell therapy (ACT) based on ex vivo expanded peripheral CTLs, tumor infiltrating lymphocytes (TILs), gene-engineered TCR- and chimeric antigen receptor (CAR)-T cells have all shown durable clinical efficacies in multiple types of cancers. However, these immunotherapeutic approaches only benefit a small fraction of cancer patients as various immune resistance mechanisms and limitations make their effective use a challenge in the majority of cancer patients. For example, adaptive resistance to therapeutic PD-1 blockade is associated with an upregulation of some additional immune checkpoint receptors. The efficacy of transferred tumor-specific T cells under the current clinical ACT protocol is often limited by their inefficient engraftment, poor persistence, and weak capability to attack tumor cells. Recent studies demonstrate that the complement receptor C3aR and C5aR function as a new class of immune checkpoint receptors. Complement signaling through C3aR and C5aR expressed on effector T lymphocytes prevent the production of the cytokine interleukin-10 (IL-10). Removing C3aR/C5aR-mediated transcriptional suppression of IL-10 expression results in endogenous IL-10 production by antitumor effector T cells, which drives T cell expansion and enhances T cell-mediated antitumor immunity. Importantly, preclinical, and clinical data suggest that a signaling axis consisting of complement/C3aR/C5aR/IL-10 critically regulates T cell mediated antitumor immunity and manipulation of the pathway ex vivo and in vivo is an effective strategy for cancer immunotherapy. Furthermore, a combination of treatment strategies targeting the complement/C3aR/C5aR/IL-10 pathway with other treatment modalities may improve cancer therapeutic efficacy.

show abstract

Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors

Cited by 615 publications

References 136 publications

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

Soft‐tissue sarcoma in adolescents and young adults compared with older adults: A report among 5000 patients from the Scandinavian Sarcoma Group Central Register

The Complement Receptors C3aR and C5aR Are a New Class of Immune Checkpoint Receptor in Cancer Immunotherapy

Contact Info

Product

Resources

About