Association between PD1 mRNA and response to anti-PD1 monotherapy across multiple cancer types

Paré, Laia; Pascual, Tomás; Seguí, Elia; Teixidó, Cristina; González‐Cao, María; Galván, Patricia; Rodriguez-Lescure, A.; Gonzalez, B.; Cuatrecasas, Míriam; Pineda, Estela; Torné, Aureli; Crespo, Guillermo; Martín‐Algarra, Salvador; Pérez-Ruiz, Elísabeth; Reig, Òscar; Viladot, Margarita; Font, Carme; Adamo, Bárbara; Vidal, María; Gaba, Lydia; Muñoz, Montserrat; Victoria, Iván; Ruiz, G. Garrido; Viñolas, Núria; Mellado, Begoña; Maurel, J.; García-Corbacho, Javier; Molina-Vila, Miguel Ángel; Juan, Manel; Llovet, Josep M.; Reguart, Noemı́; Arance, Ana; Prat, Aleix

doi:10.1093/annonc/mdy335

Cited by 83 publications

(61 citation statements)

References 16 publications

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“…PD-1 expression has also shown predictive power in evaluating the efficacy of ICI therapy [34,45]. Our study found that in most tumour types there was a positive association between the PD-1 + Tils infiltration and the PD-L1 expression ( Fig.…”

Section: Discussionsupporting

confidence: 54%

The frequency and inter-relationship of PD-L1 expression and tumour mutational burden across multiple types of advanced solid tumours in China

et al. 2020

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Background: PD-L1 expression and tumour mutational burden (TMB) are both associated with the responses of multiple tumours to immune checkpoint inhibitor (ICI) therapy. However, their prevalence and correlations may differ in different types of advanced solid tumours. Methods: PD-L1 expression, TMB, and PD-1 + Tils (tumour-infiltrating lymphocytes) infiltration and their relationships were assessed in 6668 advanced solid tumour specimens across 25 tumour types. CD8 + T cell infiltration was analysed in 347 NSCLC samples. The associations of these biomarkers with the therapeutic effect of PD-1 inhibitor were analysed in a cohort of NSCLC samples. Results: PD-L1 expression levels and TMB in different tumour types varied widely and their relationship was not significantly correlated in most cancer types, with only a small association across all specimens (Spearman R = 0.059). PD-1 + Tils infiltration was positively correlated with PD-L1 expression across all samples (Spearman R = 0.3056). However, there is no such correlation between PD-1 + Tils infiltration and TMB. In NSCLC samples, CD8 + T cell infiltration was correlated with PD-1 + Tils infiltration and PD-L1 expression but not with TMB (Spearman R = 0.4117, 0.2045, and 0.0007, respectively). Patients in the CR/PR group (anti-PD-1 therapy) had higher levels of PD-L1 expression, TMB, PD-1 + Tils, and CD8 + T cell infiltration, and many patients in this group exhibited concomitantly elevated levels of multiple biomarkers. Conclusions: Our results showed the PD-L1 expression status and TMB in various types of advanced solid tumours in Chinese patients and their relationships with PD-1 + Tils and CD8 + T cell infiltration, which may inform ICI treatment.

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Section: Discussionsupporting

confidence: 54%

The frequency and inter-relationship of PD-L1 expression and tumour mutational burden across multiple types of advanced solid tumours in China

et al. 2020

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“…The Cancer Genome Atlas data from more than 8,000 tumor samples (across 31 cancer types) revealed that PD1 mRNA may be a potential good predictor for anti‐PD1/PD‐L1 monotherapy activity .…”

Section: Resultsmentioning

confidence: 99%

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

2019

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In the light of recent advances in the immunotherapy field for breast cancer (BC) treatment, especially in the triple‐negative subtype, the identification of reliable biomarkers capable of improving patient selection is paramount, because only a portion of patients seem to derive benefit from this appealing treatment strategy. In this context, the role of programmed cell death ligand 1 (PD‐L1) as a potential prognostic and/or predictive biomarker has been intensively explored, with controversial results. The aim of the present review is to collect available evidence on the biological relevance and clinical utility of PD‐L1 expression in BC, with particular emphasis on technical aspects, prognostic implications, and predictive value of this promising biomarker. Implications for Practice In the light of the promising results coming from trials of immune checkpoint inhibitors for breast cancer treatment, the potential predictive and/or prognostic role of programmed cell death ligand 1 (PD‐L1) in breast cancer has gained increasing interest. This review provides clinicians with an overview of the available clinical evidence regarding PD‐L1 as a biomarker in breast cancer, focusing on both data with a possible direct impact on clinic and methodological pitfalls that need to be addressed in order to optimize PD‐L1 implementation as a clinically useful tool for breast cancer management.

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“…Furthermore, the reproducibility of PD-L1 detection due to its spatial and temporal heterogeneity and the different relevance as predictive markers of TC and IC positivity remains undefined. In order to overcome these gaps, new biomarkers are currently under evaluation as potential surrogates of ICI efficacy [52].…”

Section: Programmed Death Ligand 1 (Pd-l1)mentioning

confidence: 99%

Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes

Diana

Carlino

Franzese

et al. 2020

Cancers

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Triple negative breast cancers (TNBCs) are characterized by worse prognosis, higher propensity to earlier metastases, and shorter survival after recurrence compared with other breast cancer subtypes. Anthracycline- and taxane-based chemotherapy is still the mainstay of treatment in early stages, although several escalation approaches have been evaluated to improve survival outcomes. The addition of platinum salts to standard neoadjuvant chemotherapy (NACT) remains controversial due to the lack of clear survival advantage, and the use of adjuvant capecitabine represents a valid treatment option in TNBC patients with residual disease after NACT. Recently, several clinical trials showed promising results through the use of poly ADP-ribose polymerase (PARP) inhibitors and by incorporating immunotherapy with chemotherapy, enriching treatment options beyond conventional cytotoxic agents. In this review, we provided an overview on the current standard of care and a comprehensive update of the recent advances in the management of early stage TNBC and focused on the latest emerging biomarkers and their clinical application to select the best therapeutic strategy in this hard-to-treat population.

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Association between PD1 mRNA and response to anti-PD1 monotherapy across multiple cancer types

Abstract: Our study provides a clinically applicable assay that links PD1 mRNA abundance, activated CD8 T-cells and anti-PD1 efficacy.

Cited by 83 publications

References 16 publications

The frequency and inter-relationship of PD-L1 expression and tumour mutational burden across multiple types of advanced solid tumours in China

The frequency and inter-relationship of PD-L1 expression and tumour mutational burden across multiple types of advanced solid tumours in China

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes

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