Clinical response to nivolumab in an INI1-deficient pediatric chordoma correlates with immunogenic recognition of brachyury

AbstractPoorly differentiated chordoma (PDC) is a recently recognized subtype of chordoma characterized by expression of the embryonic transcription factor, brachyury, and loss of INI1. PDC primarily affects children and is associated with a poor prognosis and limited treatment options. Here we describe the molecular and immune tumour microenvironment profiles of two paediatric PDCs produced using whole-genome, transcriptome and whole-genome bisulfite sequencing (WGBS) and multiplex immunohistochemistry. Our analyses revealed the presence of tumour-associated immune cells, including CD8+ T cells, and expression of the immune checkpoint protein, PD-L1, in both patient samples. Molecular profiling provided the rationale for immune checkpoint inhibitor (ICI) therapy, which resulted in a clinical and radiographic response. A dominant T cell receptor (TCR) clone specific for a brachyury peptide–MHC complex was identified from bulk RNA sequencing, suggesting that targeting of the brachyury tumour antigen by tumour-associated T cells may underlie this clinical response to ICI. Correlative analysis with rhabdoid tumours, another INI1-deficient paediatric malignancy, suggests that a subset of tumours may share common immune phenotypes, indicating the potential for a therapeutically targetable subgroup of challenging paediatric cancers.

Download Full-text

Immune checkpoint and checkpoint inhibitors in hepatocellular carcinoma

Thai Journal of Hepatology ◽

10.30856/th.jhep2018vol1iss1_07 ◽

2018 ◽

Vol 1 (1) ◽

pp. 28-32

Author(s):

Piyawat Komolmit

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Major Histocompatibility Complex ◽

T Cell Receptor ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Cell Receptor ◽

Immune Checkpoints ◽

Histocompatibility Complex

การรักษามะเร็งด้วยแนวความคิดของการกระตุ้นให้ภูมิต้านทานของร่างกายไปทำลายเซลล์มะเร็งนั้น ปัจจุบันได้รับการพิสูจน์ชัดว่าวิธีการนี้สามารถหยุดยั้งการแพร่กระจายของเซลล์มะเร็ง โดยไม่ก่อให้เกิดภาวะแทรกซ้อนทางปฏิกิริยาภูมิต้านทานต่ออวัยวะส่วนอื่นที่รุนแรง สามารถนำมาใช้ทางคลินิกได้ ยุคของการรักษามะเร็งกำลังเปลี่ยนจากยุคของยาเคมีบำบัดเข้าสู่การรักษาด้วยภูมิต้านทาน หรือ immunotherapy ยากลุ่ม Immune checkpoint inhibitors โดยเฉพาะ PD-1 กับ CTLA-4 inhibitors จะเข้ามามีบทบาทในการรักษามะเร็งตับในระยะเวลาอันใกล้ จำเป็นแพทย์จะต้องมีความรู้ความเข้าใจในพื้นฐานของ immune checkpoints และยาที่ไปยับยั้งโมเลกุลเหล่านี้ Figure 1 เมื่อ T cells รับรู้แอนทิเจนผ่านทาง TCR/MHC จะมีปฏิกิริยาระหว่าง co-receptors หรือ immune checkpoints กับ ligands บน APCs หรือ เซลล์มะเร็ง ทั้งแบบกระตุ้น (co-stimulation) หรือยับยั้ง (co-inhibition) TCR = T cell receptor, MHC = major histocompatibility complex

Download Full-text

Checkpoint-blocker induced autoimmunity is associated with pretreatment T cell expression profiles and favourable outcome in melanoma

10.1101/2020.06.23.20138594 ◽

2020 ◽

Author(s):

W. Ye ◽

A Olsson-Brown ◽

R. A. Watson ◽

V. T. F. Cheung ◽

R. D. Morgan ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Clinical Outcome ◽

Adverse Events ◽

Metastatic Melanoma ◽

T Cell Receptor ◽

Immune Checkpoint ◽

Single Agent ◽

Cell Receptor ◽

Pre Treatment

1Abstract1.1BackgroundImmune checkpoint blockers (ICBs) activate CD8+ T cells to elicit anti-cancer activity but frequently lead to immune-related adverse events (irAEs). The relationship of irAE with baseline parameters and clinical outcome is unclear. We investigated associations between irAE development, CD8+ T cell receptor diversity and expression and clinical outcome in a non-trial setting.1.2MethodsPatients ≥18 years old with metastatic melanoma (MM) receiving combination ICB (ipilimumab plus nivolumab – cICB, n=60) or single-agent ICB (nivolumab/pembrolizumab – sICB, n=78) were prospectively recruited. We retrospectively evaluated the impact of irAEs on survival. This analysis was repeated in an independent cohort of MM patients treated at a separate institution (n=210, cICB:74, sICB:136). We performed RNA sequencing of CD8+ T cells isolated from patients prior to treatment, analysing T cell receptor clonality differential transcript expression according to irAE development.1.3Results48.6% of patients experienced treatment-related irAEs within the first 5 cycles of treatment. Development of irAE prior to the 5th cycle of ICB was associated with longer progression-free and overall survival (PFS, OS) in the primary cohort (log-rank test, PFS: P=0.00034; OS: P<0.0001), replicated in the secondary cohort (OS: P=0.00064). Across cohorts median survival for those patients not experiencing irAE was 14.4 (95% CI:9.6-19.5) months vs not-reached (95% CI:28.9 - Inf), P=3.0×10−7. Pre-treatment performance status and neutrophil count, but not BMI, were additional predictors of clinical outcome. Analysis of CD8+ T cells from 128 patients demonstrated irAE development was associated with increased T cell receptor diversity post-treatment (P=4.3×10−5). Development of irAE in sICB recipients was additionally associated with baseline differential expression of 224 transcripts (FDR<0.1), enriched in pro-inflammatory pathway genes including CYP4F3 and PTGS2.1.4ConclusionsEarly irAE development post-ICB is strongly associated with favourable survival in MM and increased diversity of peripheral CD8+ T cell receptors after treatment. irAE post-sICB is associated with pre-treatment upregulation of inflammatory pathways, indicating irAE development may reflect baseline immune activation states.Key messageImmune-related adverse events (irAEs) commonly occur in patients with metastatic melanoma treated with immune checkpoint blockade (ICB) therapy. In real world setting we find development of early irAEs post-ICB treatment is associated with survival benefit, indicative of a shared mechanism with anti-tumour efficacy. CD8+ T cells from patients who develop irAE show increased receptor diversity, and pre-treatment samples from patients who develop irAE post single-agent anti-PD1 show over-expression of inflammatory pathways, indicating baseline immune state can determine irAE development.

Download Full-text

Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy

Biochemical Society Transactions ◽

10.1042/bst20150291 ◽

2016 ◽

Vol 44 (2) ◽

pp. 412-418 ◽

Cited By ~ 79

Author(s):

Oladapo O. Yeku ◽

Renier J. Brentjens

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Receptor ◽

Second Generation ◽

Cell Receptor ◽

Tumour Microenvironment ◽

Interleukin 12 ◽

Car T Cells ◽

Car T Cell ◽

Car T

Chimaeric antigen receptor (CAR) T-cells are T-cells that have been genetically modified to express an artificial construct consisting of a synthetic T-cell receptor (TCR) targeted to a predetermined antigen expressed on a tumour. Coupling the T-cell receptor to a CD3ζ signalling domain paved the way for first generation CAR T-cells that were efficacious against cluster of differentiation (CD)19-expressing B-cell malignancies. Optimization with additional signalling domains such as CD28 or 4-1BB in addition to CD3ζ provided T-cell activation signal 2 and further improved the efficacy and persistence of these second generation CAR T-cells. Third generation CAR T-cells which utilize two tandem costimulatory domains have also been reported. In this review, we discuss a different approach to optimization of CAR T-cells. Through additional genetic modifications, these resultant armored CAR T-cells are typically modified second generation CAR T-cells that have been further optimized to inducibly or constitutively secrete active cytokines or express ligands that further armor CAR T-cells to improve efficacy and persistence. The choice of the ‘armor’ agent is based on knowledge of the tumour microenvironment and the roles of other elements of the innate and adaptive immune system. Although there are several variants of armored CAR T-cells under investigation, here we focus on three unique approaches using interleukin-12 (IL-12), CD40L and 4-1BBL. These agents have been shown to further enhance CAR T-cell efficacy and persistence in the face of a hostile tumour microenvironment via different mechanisms.

Download Full-text

Immunogenomic profile of colorectal cancer response to immune checkpoint blockade

10.1101/2020.12.15.422831 ◽

2020 ◽

Author(s):

Michele Bortolomeazzi ◽

Mohamed Reda Keddar ◽

Lucia Montorsi ◽

Amelia Acha-Sagredo ◽

Lorena Benedetti ◽

...

Keyword(s):

Colorectal Cancer ◽

T Cells ◽

Immune Checkpoint ◽

Immune Escape ◽

Cell Receptor ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Critical Threshold ◽

Mutational Burden ◽

Antigen Presenting

To dissect the determinants of the heterogeneous response of colorectal cancer (CRC) to immune checkpoint blockade, we profile tumour and immune infiltrates of 721 cancer regions from 29 patients treated with Pembrolizumab or Nivolumab. Combining multi-regional whole exome, RNA and T-cell receptor sequencing we show that anti-PD1 agents are most effective in CRCs with high mutational burden and low activation of the WNT pathway. However, above a critical threshold defining the hypermutated phenotype, response is no longer associated with mutational burden but rather with high clonality of immunogenic mutations, expanded T cells and active immune escape mechanisms. Using high-dimensional imaging mass cytometry and multiplexed immunofluorescence, we observe that responsive hypermutated CRCs are rich in cytotoxic and proliferating PD1-expressing CD8 infiltrates interacting with high-density clusters of PDL1-expressing antigen presenting macrophages. We propose that anti-PD1 agents release the PD1-PDL1 interaction between CD8 T cells and macrophages thus promoting their expansion in intra-tumour niches.

Download Full-text

Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells

10.21203/rs.2.12812/v3 ◽

2019 ◽

Author(s):

Kazushige Yoshida ◽

Masanori Okamoto ◽

Jun Sasaki ◽

Chika Kuroda ◽

Haruka Ishida ◽

...

Keyword(s):

T Cells ◽

Cell Lines ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Tumour Volume ◽

Tumour Microenvironment ◽

Osteosarcoma Cell

Abstract Background: There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear. Methods: In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFNγ for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumour by flowcytometry. Results: We discovered that IFNγ increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumour microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes. Conclusions: Here we clarify for the first time an additional mechanism of anti-tumour effect—as exerted by anti-PD-1 antibody decreasing Treg— we anticipate that our findings will lead to the development of new methods for cancer treatment.

Download Full-text

Rapid and Sustained Increase of LGL and Rare CMV-Reactivation During Dasatinib Treatments in CML

Blood ◽

10.1182/blood.v118.21.2752.2752 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2752-2752

Author(s):

Hideo Tanaka ◽

Shizuka Nakashima ◽

Miyuki Usuda

Keyword(s):

T Cells ◽

Clinical Response ◽

Conflicts Of Interest ◽

Γδ T Cells ◽

Oral Intake ◽

Cell Receptor ◽

Myelogenous Leukemia ◽

Pleural Effusions ◽

Total Lymphocyte ◽

Cmv Reactivation

Abstract Abstract 2752 Dasatinib has extensive inhibition profile on multiple kinases. Clonal expansion of large granular lymphocyte (LGL) is a noteworthy off-target phenomenon. In this study, we investigated the increase of LGL in peripheral blood during dasatinib treatments which were changed from imatinib treatments, in 25 chronic myelogenous leukemia (CML) patients in CP or AP. METHODS: The criteria of the LGL-increase was set by “increase of lymphocytes over 3,000/μL, and increase of LGL count over 1,500/μL” was found during the course of the treatment. Flow cytometry analyses were performed during the treatments in all cases, and also before the dasatinib treatments in 17 cases. T-cell receptor (TCR) clonal rearrangements for TCR-β, -γ, and -δ, were examined by PCR-based method during the treatments in all cases. Furthermore, comparison of LGL counts before and 2 hours after oral intake were investigated in all 25 cases. CMV activations were assessed in all cases by serum CMV-IgG, serum CMV-IgM, and by “CMV antigen test Teijin (HRP-C7)” which can detect CMV pp65 antigen in leukocytes. RESULTS: Median follow-up time was 11 months (range 3–28). (1) Fifteen out of the 25 patients (60%) showed increase of LGL, which had not been observed during preceding imatinib treatments. Median time until LGL count reached 1,500/μL was 11 weeks (range 6–44), and increased-LGL sustained as far as dasatinib was continued. In these 15 patients, all showed increase of CD56+, CD16+, CD3- NK-cells, and 11 patients also showed increase of CD3+, CD8+, CD4- T-cells. Evident increase of γδ-T cells was not observed. Clonal rearrangements of TCR-β gene were observed in 13 of 15 (87%), and TCR-γ in 12 (80%), and TCR-δ in 9 (60%) patients. Pleural effusions were observed in 9 out of 15 (60%) patients. Regarding clinical response, 4 cases newly achieved CMR, 7 maintained CMR (totally 73% achieved or maintained CMR), and 3 achieved or maintained MMR. (2) On the other hand, 10 out of 25 patients (40%) did not show increase of LGL. In these 10 patients, clonal rearrangements of TCR-β gene were observed in 4 of 10 (40%), and TCR-γ in 3 (30%), and TCR-Δ in 4 (40%) patients. Three patients showed no clonality for all the three TCR genes. Pleural effusions were observed in 2 out of 10 (20%) patients. Regarding clinical response, no case newly achieved CMR, 5 maintained CMR (totally 50% achieved or maintained CMR), and 4 achieved or maintained MMR. (3) LGL counts increased 2 hours after intake of dasatinib in all patients. Regarding the 15 patients who showed LGL increase during the treatment courses, LGL counts were 1,349±918/μL (mean±SD)(before), and 2,895±2,240/μL (2 hours after), indicating 2.1 times increase (P=0.006); total lymphocyte counts were 2,153±1,129/μL (before), and 4,456±3,219/μL (after), indicating 2.1 times increase (P=0.01). Regarding the 10 patients who did not show LGL increase during the treatment courses, LGL counts were 422±384/μL (before), and 805±419/μL (after), indicating 1.9 times increase (P=0.02); total lymphocyte counts were 1,094±556/μL (before), and 1,859±899/μL (after), indicating 1.7 times increase (P=0.03). (4) In the total 25 patients, serum CMV-IgM were negative in most of the cases (23 of 25; 92%). CMV HRP-C7 were completely negative (meaning undetectable) in most of the cases (23 of 25; 92%), and it was barely positive only in 2 cases (1 cell and 2 cells were positive out of ∼60,000 leukocytes examined, respectively). CONCLUSION: LGL lymphocytosis occurred in 60% of patients, which seems to be related with favorable molecular responses, and with relatively high incidence of pleural effusions. The TCR gene rearrangements were observed in both groups, but higher in the increase-LGL group than the non-increase-LGL group. Approximately 2-times rapid increase of LGL and total lymphocytes were observed 2 hours after intake of dasatinib, in all the patients, irrespective of the LGL-increase during the treatment courses. In the clinical setting, evident immunodeficiency was not observed in terms of CMV-reactivation. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Emerging Next-Generation Target for Cancer Immunotherapy Research: The Orphan Nuclear Receptor NR2F6

Cancers ◽

10.3390/cancers13112600 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2600

Author(s):

Victoria Klepsch ◽

Kerstin Siegmund ◽

Gottfried Baier

Keyword(s):

T Cells ◽

Nuclear Receptor ◽

Immune Checkpoint ◽

Immune Therapy ◽

Treatment Options ◽

Orphan Nuclear Receptor ◽

Oncology Research ◽

Gene Ablation ◽

Surface Receptor ◽

Promising Perspective

Additional therapeutic targets suitable for boosting anti-tumor effector responses have been found inside effector CD4+ and CD8+ T cells. It is likely that future treatment options will combine surface receptor and intracellular protein targets. Utilizing germline gene ablation as well as CRISPR/Cas9-mediated acute gene mutagenesis, the nuclear receptor NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) has been firmly characterized as such an intracellular immune checkpoint in effector T cells. Targeting this receptor appears to be a strategy for improving anti-tumor immunotherapy responses, especially in combination with CTLA-4 and PD-1. Current preclinical experimental knowledge firmly validates the immune checkpoint function of NR2F6 in murine tumor models, which provides a promising perspective for immunotherapy regimens in humans in the near future. While the clinical focus remains on the B7/CD28 family members, protein candidate targets such as NR2F6 are now being investigated in laboratories around the world and in R&D companies. Such an alternative therapeutic approach, if demonstrated to be successful, could supplement the existing therapeutic models and significantly increase response rates of cancer patients and/or expand the reach of immune therapy regimens to include a wider range of cancer entities. In this perspective review, the role of NR2F6 as an emerging and druggable target in immuno-oncology research will be discussed, with special emphasis on the unique potential of NR2F6 and its critical and non-redundant role in both immune and tumor cells.

Download Full-text

Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells

BMC Cancer ◽

10.1186/s12885-019-6499-y ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 5

Author(s):

Kazushige Yoshida ◽

Masanori Okamoto ◽

Jun Sasaki ◽

Chika Kuroda ◽

Haruka Ishida ◽

...

Keyword(s):

T Cells ◽

Cell Lines ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Tumour Volume ◽

Tumour Microenvironment ◽

Osteosarcoma Cell

Abstract Background There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear. Methods In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFNγ for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumour by flowcytometry. Results We discovered that IFNγ increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumour microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes. Conclusions Here we clarify for the first time an additional mechanism of anti-tumour effect—as exerted by anti-PD-1 antibody decreasing Treg— we anticipate that our findings will lead to the development of new methods for cancer treatment.

Download Full-text

T-cell CX3CR1 expression as a dynamic blood-based biomarker of response to immune checkpoint inhibitors

Nature Communications ◽

10.1038/s41467-021-21619-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Takayoshi Yamauchi ◽

Toshifumi Hoki ◽

Takaaki Oba ◽

Vaibhav Jain ◽

Hongbin Chen ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Dynamic Change ◽

Cell Subset ◽

Cell Receptor ◽

Durable Response ◽

Cx3cr1 Expression

AbstractImmune checkpoint inhibitors (ICI) have revolutionized treatment for various cancers; however, durable response is limited to only a subset of patients. Discovery of blood-based biomarkers that reflect dynamic change of the tumor microenvironment, and predict response to ICI, will markedly improve current treatment regimens. Here, we investigate CX3C chemokine receptor 1 (CX3CR1), a marker of T-cell differentiation, as a predictive correlate of response to ICI therapy. Successful treatment of tumor-bearing mice with ICI increases the frequency and T-cell receptor clonality of the peripheral CX3CR1+CD8+ T-cell subset that includes an enriched repertoire of tumor-specific and tumor-infiltrating CD8+ T cells. Furthermore, an increase in the frequency of the CX3CR1+ subset in circulating CD8+ T cells early after initiation of anti-PD-1 therapy correlates with response and survival in patients with non-small cell lung cancer. Collectively, these data support T-cell CX3CR1 expression as a blood-based dynamic early on-treatment predictor of response to ICI therapy.

Download Full-text

A novel antibody targeting ICOS increases intratumoural cytotoxic to regulatory T cell ratio and induces tumour regression

10.1101/771493 ◽

2019 ◽

Cited By ~ 1

Author(s):

Richard C.A. Sainson ◽

Anil K. Thotakura ◽

Miha Kosmac ◽

Gwenoline Borhis ◽

Nahida Parveen ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Tumour Response ◽

Tumour Microenvironment ◽

Tumour Regression ◽

Transgenic Mouse Line ◽

Variable Domains ◽

Immune Contexture

AbstractThe immunosuppressive tumour microenvironment constitutes a significant hurdle to the response to immune checkpoint inhibitors. Both soluble factors and specialised immune cells such as regulatory T cells (TReg) are key components of active intratumoural immunosuppression. Previous studies have shown that Inducible Co-Stimulatory receptor (ICOS) is highly expressed in the tumour microenvironment, especially on TReg, suggesting that it represents a relevant target for preferential depletion of these cells. Here, we used immune profiling of samples from tumour bearing mice and cancer patients to characterise the expression of ICOS in different tissues and solid tumours. By immunizing an Icos knockout transgenic mouse line expressing antibodies with human variable domains, we selected a fully human IgG1 antibody called KY1044 that binds ICOS from different species. Using KY1044, we demonstrated that we can exploit the differential expression of ICOS on T cell subtypes to modify the tumour microenvironment and thereby improve the anti-tumour immune response. We showed that KY1044 induces sustained depletion of ICOShigh TReg cells in mouse tumours and depletion of ICOShigh T cells in the blood of non-human primates, but was also associated with secretion of pro-inflammatory cytokines from ICOSlow TEFF cells. Altogether, KY1044 improved the intratumoural TEFF:TReg ratio and increased activation of TEFF cells, resulting in monotherapy efficacy or in synergistic combinatorial efficacy when administered with the immune checkpoint blocker anti-PD-L1. In summary, our data demonstrate that targeting ICOS with KY1044 can favourably alter the intratumoural immune contexture, promoting an anti-tumour response.

Download Full-text