Αρχική World News A Peripheral Immune Signature of Responsiveness to PD-1 Blockade in cHL

A Peripheral Immune Signature of Responsiveness to PD-1 Blockade in cHL

Findings from a translational analysis of CheckMate 205 study indicate that anti-PD-1 therapy was most effective in patients with classical Hodgkin lymphoma (cHL) who had a diverse baseline T cell receptor (TCR) repertoire. X. Shirley Liu and Margaret A. Shipp of the Dana-Farber Cancer Institute in Boston, MA, USA and colleagues, who published their results on 10 August 2020 in the Nature Medicine, wrote that CD4+, but not CD8+, TCR diversity significantly increased during the therapy and most strikingly in patients who had achieved complete responses (CRs). In addition, the patients who responded to therapy had an increased abundance of activated natural killer (NK) cells and a newly identified CD3CD68+CD4+GrB+ subset.

The authors wrote in the study background that cHL includes rare malignant Hodgkin Reed–Sternberg (HRS) cells mixed with abundant inflammatory and immune cells. Although the cHL inflammatory infiltrate is rich in T cells, it is not associated with an effective anti-tumour immune response.

The investigators previously identified near-universal copy-number gains of PD-L1 and PD-L2 on chromosome 9p24.1, and copy-number-dependent increased expression of the PD-1 ligands on HRS cells. PD-1 ligands engage PD-1-receptor-positive T cells and induce T cell exhaustion, which can be abrogated by PD-1 blockade.

Patients with relapsed/refractory cHL, who have a genetic basis for enhanced PD-1 signalling, also exhibit the highest reported response rates to PD-1 blockade. Multiple PD-1 antibodies have been approved for the treatment of relapsed/refractory cHL and incorporated into front line clinical trials. Despite these genetic observations and rapid clinical translation, the precise mechanism of action of PD-1 blockade in cHL remains undefined.

In certain solid tumours, PD-1 blockade increases the activity of CD8+ cytotoxic T cells in the tumour microenvironment (TME). However, HRS cells frequently lack cell-surface expression of β2 microglobulin (B2M) and major histocompatibility complex (MHC) class I owing to inactivating mutations of B2M or copy loss of B2M or MHC class I genes. As MHC-class-I-mediated tumour antigen presentation is essential for recognition by CD8+ T cells, these findings implicate non-CD8+ effector mechanisms of PD-1 blockade in cHL.

MHC-class-II-mediated antigen presentation to CD4+ effector cells also plays an important role in anti-tumour immunity. HRS cells are often MHC class II-positive, likely reflecting their lineage from MHC class II-positive B cells in the germinal centre. In intact tumours, PD-L1-positive HRS cells are also more likely to be in physical contact with PD-1-positive CD4+ T cells than with PD-1-positive CD8+ T cells. The previous single-cell analyses of primary cHL cell suspensions also revealed a CD4+ T-cell-rich TME with expanded numbers of T-helper 1-polarised effectors and regulatory T cells.

Consistent with these observations, the same team also found that expression of MHC class II, but not MHC class I, in HRS cells was associated with responses to PD-1 inhibitor nivolumab in patients with relapsed/refractory cHL. Additional evidence of non-MHC-restricted immune mechanisms came from patients who achieved short-lived CRs to anti-PD-1 blockade although their HRS cells lacked expression of β2M, MHC class I and MHC class II.

Recent studies in murine models and patients with certain solid tumours associate circulating immune cell subsets with responses to checkpoint blockade.

In this translational study, the study team utilised complementary approaches, TCR sequencing and cytometry by time-of-flight (CyTOF) analyses, to characterise the peripheral immune signature of patients with relapsed/refractory cHL who received anti-PD-1 therapy. In particular, they tried to obtain a peripheral immune signature of responsiveness to PD-1 blockade in 56 patients treated in the CheckMate 205 phase II clinical trial. It was a non-comparative, multicohort, single arm, open-label study of nivolumab in cHL (NCT02181738).

The study investigators found that anti-PD-1 therapy was most effective in patients with a diverse baseline TCR repertoire and an associated expansion of singleton clones during treatment. CD4+, but not CD8+, TCR diversity significantly increased during therapy, most strikingly in patients who had achieved complete responses. Additionally, patients who responded to therapy had an increased abundance of activated NK cells and a newly identified CD3CD68+CD4+GrB+ subset.

The authors concluded that their results highlight the roles of recently expanded, clonally diverse CD4+ T cells and innate effectors in the efficacy of PD-1 blockade in cHL.

This work was supported in part by Bloodwise Fellowship, Helen Gurley Brown Fellowship, the US National Institutes of Health grants, the Miller Family Fund and the BMS International Immuno-Oncology Network.

Reference

Cader FZ, Hu X, Goh WL, et al. A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphomaNat Med; Published online 10 August 2020. DOI: https://doi.org/10.1038/s41591-020-1006-1

Source

NEWSLETTER

Συμπληρώστε το email σας για να λαμβάνετε τις σημαντικότερες ειδήσεις από το ogkologos.com

Βρείτε μας

2,449ΥποστηρικτέςΚάντε Like
57ΑκόλουθοιΑκολουθήστε

Διαβαστε Επίσης

ΕΞΕΛΙΞΕΙΣ ΣΤΗ ΘΕΡΑΠΕΙΑ ΤΟΥ ΜΗ-ΜΙΚΡΟΚΥΤΤΑΡΙΚΟΥ ΚΑΡΚΙΝΟΥ ΤΟΥ ΠΝΕΥΜΟΝΑ (ΜΜΚΠ)

ΕΞΕΛΙΞΕΙΣ ΣΤΗ ΘΕΡΑΠΕΙΑ ΤΟΥ ΜΗ-ΜΙΚΡΟΚΥΤΤΑΡΙΚΟΥ ΚΑΡΚΙΝΟΥ ΤΟΥ ΠΝΕΥΜΟΝΑ (ΜΜΚΠ) Γράφει ο Δρ Παπαδούρης Σάββας, Παθόλογος-Ογκολόγος   Ο ΜΜΚΠ βρίσκεται αναλογικά στο 80% και πλέον του συνολικού...

Διατρέχουν όντως οι καρκινοπαθείς μεγαλύτερο κίνδυνο λόγω κοροναϊού;

Σε πρακτικό επίπεδο, τα δεδομένα των σχετικών μελετών υποδηλώνουν ότι η χημειοθεραπεία ή οι άλλες αντι-νεοπλασματικές θεραπείες δεν αυξάνουν σημαντικά τον κίνδυνο θνησιμότητας από...

FDA: Η ακτινοβολία των smartphones δεν προκαλεί καρκίνο

Σε μια νέα έκθεσή της, η Υπηρεσία Τροφίμων και Φαρμάκων (FDA) των ΗΠΑ αναφέρει ότι επανεξέτασε τις σχετικές επιστημονικές έρευνες που δημοσιεύθηκαν τα τελευταία...

Νέα ανακάλυψη, νέα ελπίδα για τον καρκίνο

Ένα νεοανακαλυφθέν τμήμα του ανοσοποιητικού μας συστήματος θα μπορούσε να αξιοποιηθεί για την αντιμετώπιση όλων των ειδών καρκίνου, σύμφωνα με επιστήμονες του πανεπιστημίου Cardiff...

Καρκίνος: Ευεργετική για τους καρκινοπαθείς η άσκηση

Σημαντικά ωφέλη προσφέρει η άσκηση, ακόμη και σε ασθενείς με καρκίνο. Οι περισσότεροι ασθενείς αγνοούν τα οφέλη που μπορεί να έχει γι’ αυτούς η συχνή...

Prostate Cancer

The article is provided by Scientific Communications Officer of NIPD Genetics, Ms Marina Charitou (MSc) Prostate Cancer Awareness Prostate cancer is the second most common cancer...
- Advertisment -

Ροή Ειδήσεων

EMA Recommends Granting a Marketing Authorisation for Lenalidomide Mylan

On 15 October 2020, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting...

Easy Meals at Home

Our theme this week is delicious, easy to make, at home meals. These recipes minimize your cook time and maximize your food enjoyment. Ingredients 8...

This Saturday: National Prescription Drug Take-Back Day

Have you taken a look at your medicine cabinet lately? Aside from cotton swabs, mouthwash and makeup remover, are there old, outdated prescription drugs...

How People With Cancer Can Benefit From Online Therapy

Tanya J. Peterson, MS, is credentialed with the National Board of Certified Counselors. She is a regular contributor to the mental health website, Choosing...

EMA Recommends Granting a Conditional Marketing Authorisation for Autologous Anti-CD19-Transduced CD3+ Cells

On 15 October 2020, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting...

New Treatment Helps Survivors Regain Sensation After Breast Cancer

When NBC’s Kristen Dahlgren was diagnosed with breast cancer, she didn’t think much about the lack of sensation that her mastectomy would likely leave...