6077 Background: Treatment optimization in HPV-associated oropharyngeal cancer (OPSCC) remains challenging due to the limited results of de-escalation trials. Existing patient selection criteria, mainly based on smoking history and TNM classification are insufficient and highlight the urgent need for standardized prognostic biomarkers. Herein, we present the first validation of the Immunoscore (IS) as a prognostic stratification tool in HPV-associated OPSCC. Methods: A cohort of 191 HPV-associated (p16⁺ and HPV DNA/RNA⁺) OPSCC patients treated between 2015–2024 was analyzed, including a French training cohort ( N = 48) and three independent validation cohorts: a French retrospective monocentric ( N = 48), a French prospective multicenter ( N = 50) and a US retrospective multicenter cohort ( N = 45). IS, an IHC-based standardized clinical digital pathology assay, quantifies CD3⁺ and CD8⁺ cell densities in tumor cores and invasive margins of FFPE sections. IS cut-offs were defined using the 25 th percentile of immune cell density in the training cohort and subsequently validated across all cohorts. Associations with disease-free survival (DFS), time to recurrence (TTR), and overall survival (OS) were assessed, along with immune profiling by 3′RNA-seq and sequential immunofluorescence. Results: Median age 65; 80% male; 74% smokers; 66% T1-2; 82% N0-1 (AJCC 8 th ). Treatments included surgery only (9%), radiotherapy ± chemotherapy (27%) and surgery + radiotherapy ± chemotherapy (64%). 52.4% were IS-High ( N = 100) and 47.6% IS-Low ( N = 91). IS-High patients showed significantly improved DFS, consistently across the training and validation cohorts 1-3 (log-rank P = 0.0004, 0.003, 0.006, and 0.001, respectively). Multivariable analysis identified IS-Low as the strongest independent risk factor for DFS (HR 9.27; 95% CI: 4.14-20.76; P < 0.001), outperforming smoking status, T/N stage, and treatment modality. The model combining IS with clinical factors showed higher predictive accuracy for DFS (C-index 0.82) than clinical variables alone (0.70; P < 0.0001). Similar strong prognostic value of IS was observed for TTR (HR 7.64; 95% CI: 3.37-17.33; P < 0.001) and OS (HR 7.26; 95% CI: 2.77-18.99; P < 0.001). IS-High tumors showed enrichment of lymphoid and myeloid immune cell populations, contrasting with immune-poor signatures in IS-Low tumors (all P < 0.05). Conclusions: IS is a robust biomarker that outperforms standard clinical variables in both prognostic and predictive accuracy. The enriched cytotoxic immune infiltrate in IS-High tumors explains favorable outcomes and supports their potential suitability for treatment de-escalation. Prospective validation in future trials is warranted.

Long considered transcriptional noise, noncoding RNAs (ncRNAs), including microRNAs and long noncoding RNAs (lncRNAs), are now recognized as central regulators of cellular function, acting as scaffolds, structural elements, and regulators of gene expression. This expanding functional landscape is reshaping our understanding of cancer biology, immune regulation, and the limits of translation itself. Beyond gene regulation, lncRNAs may be implicated in the earliest stages of oncogenic transformation, orchestrating molecular reprogramming and remodeling of the immune microenvironment in premalignant lesions. Their functional analysis has further exposed an unexpected translational dimension with some lncRNAs harboring open reading frames encoding micropeptides. These cryptic micropeptides constitute an underexplored dimension of the immunopeptidome that could shape T-cell development and antitumor immunity, with implications for cancer immunosurveillance and therapeutic targeting. Collectively, these findings call for a revised molecular dogma in which the noncoding genome is recognized as a major regulator of cellular function, oncogenic transformation, and immune surveillance.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, providing durable and even curative responses. However, most patients do not respond and current biomarkers (eg, programmed death 1 ligand 1 [PD-L1]), mismatch repair deficiency [dMMR]/high microsatellite instability [MSI] and tumor mutational burden) lack predictive accuracy. Ex vivo profiling of patient-derived tumor fragments shows promise as a predictive biomarker but relies on substantial surgical tissue to mitigate intra-specimen heterogeneity. Innovations are needed that address these challenges, particularly where limited tissue is available such as in core needle biopsies (CNBs). Live tumor fragments (LTFs) were generated from 59 human tumor resections and 31 CNBs from patients enrolled in observational clinical trials (ClinicalTrials.gov identifiers: NCT05478538, NCT05520099, NCT06349642) to assess cytokine induction following ICI treatment. LTFs were encapsulated in hydrogel and cultured ex vivo for up to 72 hours. A sequential treatment strategy that applies control and treatment within the same well was used with response to ICI or αCD3/αCD28 assessed using a multiplex secretome assay. Viability was assessed using established metabolic assays and dynamic optical coherence microscopy. LTFs maintained viability and retained T cells responsive to stimulation throughout ex vivo culture. Multiplex immunofluorescence and immunohistochemistry showed key components of the tumor microenvironment, including relative proportions of CD4+ and CD8+ immune cell populations, were preserved. Specimens positive for PD-L1 or dMMR/MSI-high were enriched for cytokine upregulation, including T-cell response cytokines IFNγ and CXCL10, after αPD-1 treatment. To demonstrate clinical applicability of the sequential treatment strategy, CNBs from patients with lung, gastrointestinal or kidney cancer were profiled and differential cytokine induction in response to ICI treatment was observed. The novel ex vivo platform presented is capable of detecting T-cell response to ICI treatment by using a sequential treatment strategy. This approach addresses challenges associated with cross-well heterogeneity in tissue composition and requires half as much tissue as a cross-well comparison, mitigating tissue limitations typically associated with non-surgical biopsies. Importantly, the platform is compatible with established functional assays as well as non-destructive spatial imaging, enabling researchers to characterize response to ICI longitudinally. Ongoing trials will enable clinicians to assess platform performance in predicting response to immunotherapy.

Early cancer detection and prophylactic intervention remain the primary strategies for reducing colorectal carcinoma incidence and mortality. Although the immune microenvironment and tumor-associated antigens have been shown to play a pivotal role in carcinogenesis, the factors shaping immune dynamics during the premalignant phase remain poorly understood. In this study, we performed a comprehensive multimodal characterization of the immune microenvironment in 258 longitudinal premalignant colorectal lesions. Using a discovery cohort of 135 lesions from 26 patients stratified by low versus high polyp development rate, we identified distinct immune states associated with polyp burden. These findings were validated in an independent cohort of 123 lesions from 43 patients. Lesions from patients with low polyp development rates exhibited signatures of robust immune surveillance characterized by enhanced adaptive immune infiltration, including defined T cell subsets, and a higher prevalence of mature tertiary lymphoid structures compared with lesions from patients with high polyp frequency. These immune features were accompanied by increased expression of noncoding RNAs. These transcripts were predicted to encode noncanonical antigens with high MHC-I (major histocompatibility complex class I) binding affinity, potentially increasing lesion immunogenicity. We propose that early carcinogenesis is shaped by the immune microenvironment in association with noncoding RNAs, revealing potential early biomarkers in individuals at high risk of developing colorectal cancer.

Background: Liver metastases (LMs) are related to poor efficacy of immune checkpoint inhibitor (ICI)-containing therapies. In the AtezoTRIBE trial, Immunoscore-Immune-Checkpoint (immunoscore-IC) was a predictor of benefit from atezolizumab in mismatch repair-proficient (pMMR) metastatic colorectal cancer (mCRC). Patients and methods: In pMMR patients enrolled in the AtezoTRIBE study, we investigated the association of LMs with immune-related biomarkers and treatment outcomes, and the predictive role of immunoscore-IC in the LMs group. Results: Out of 202 pMMR patients, 151 (75%) had LMs. No differences in immune-related features were observed according to the presence or not of LMs, except for a lower prevalence of tumour-infiltrating lymphocytes-high tumours in the LMs group (33% versus 52%, P = 0.03). Worse outcomes were observed among patients with LMs [progression-free survival (PFS), P = 0.002; overall survival (OS), P = 0.011], also in multivariable models. The effect of adding atezolizumab to FOLFOXIRI/bevacizumab was independent from LMs in terms of PFS (Pint = 0.990) and OS (Pint = 0.800). Among patients with pMMR mCRC and LMs, those with immunoscore-IC-high but not those with immunoscore-IC-low tumours achieved benefit from atezolizumab, though in the absence of a statistically significant interaction effect (Pint for PFS and OS = 0.166 and 0.473, respectively). Conclusions: LMs are associated with poor prognosis in pMMR mCRC and do not predict resistance to the addition of atezolizumab to FOLFOXIRI/bevacizumab. Immunoscore-IC seems to retain its predictive impact also among patients with LMs.

Baseline characteristics of patients according to the predefined and optimized DetermaIO score positivity cut-point in the pMMR tumours group.

The treatment of patients with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) remains a significant clinical challenge. Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), induces immunogenic cell death, potentially synergizing with immune checkpoint inhibitors. The phase 2, proof-of-concept, single-arm AVETUXIRI trial (ClinicalTrials.gov: NCT03608046) evaluates the safety and efficacy of cetuximab, irinotecan (a topoisomerase I inhibitor), and avelumab (an anti-programmed cell death ligand 1 [PD-L1]) in 57 patients with RAS wild-type or mutated MSS mCRC refractory to chemotherapy and anti-EGFR mAbs. Exploratory objectives include investigating the tumor immune microenvironment within mCRC biopsies performed during the trial and correlating it with treatment activity. A manageable safety profile is observed. Although the overall efficacy endpoints are not met, biomarkers associated with clinical efficacy are identified. Patients exhibiting a high Immunoscore, strong cytotoxic and T cell proximity to tumor cells, and a high genetic immunoediting score within mCRC biopsies before treatment demonstrate significant therapeutic survival benefit, independent of RAS tumor mutation status.

PURPOSE Immunoscore (IS) and circulating tumor DNA (ctDNA) are two emerging technologies in improving prognostication and tailoring adjuvant treatments in patients resected from a stage III colon cancer (CC). Here, we analyzed the prognostic value of the two biomarkers in patients who participated in the randomized phase III IDEA-France and HORG trials. METHODS Plasma samples were collected after surgery and before adjuvant chemotherapy. ctDNA analysis was performed using a clinically validated, personalized, tumor-informed 16-plex protein chain reaction assay. Multivariable analyses for time to recurrence (TTR; patients without recurrence or death due to CC) and overall survival (OS) were performed using ctDNA and IS results, along with other parameters including treatment duration and disease risk group. RESULTS Of the 554 patients with available ctDNA results, 445 were ctDNA-negative (80.3%) and 109 were ctDNA-positive (19.7%); baseline characteristics showed more T4/N2 and venous embolism/lymphatic invasion/perineural invasion+ in ctDNA-positive patients. With a median follow-up of 6.7 years, the 2-year TTR rate was 43.5% (95% CI, 34.1 to 52.6) for ctDNA-positive patients and 88.1% (95% CI, 84.7 to 90.8) for ctDNA-negative patients ( P < .0001). ctDNA was confirmed as an independent prognostic marker for both TTR (adjusted hazard ratio [adjHR], 5.21 [95% CI, 3.59 to 7.58]; P < .001) and OS (adjHR, 4.84 [95% CI, 3.40 to 6.89]; P < .001). ctDNA remained the most significant prognostic factor irrespective of disease stage, treatment duration, and IS results. IS was not prognostic in ctDNA-positive patients but remained a significant prognostic tool for ctDNA-negative patients. CONCLUSION In this combined analysis of two adjuvant trials dedicated to patients with stage III CC after surgery, ctDNA was detectable in 19.7% of the patients and was confirmed as a major independent prognostic biomarker. IS seems to bring additional prognostic information in the 80.3% of patients who are ctDNA-negative.

The genetic reprogramming of T cells with chimeric antigen receptors (CAR) specifically targeting CD19 in B-cell malignancies or B-cell maturation antigen for plasma cell tumors has achieved remarkable success. CAR T-cell therapy represents a revolutionary strategy in personalized cancer care, leveraging the immune system's precision to target cancer cells with unprecedented efficacy. However, challenges persist, with resistance and relapse occurring in hematologic malignancies. Understanding the intricate mechanisms governing response and resistance is crucial, emphasizing factors such as pharmacokinetics, product attributes, and tumor biology. This review focuses on biomarkers associated with CAR T-cell therapy in mature B-cell non-Hodgkin lymphoma malignancies, underscoring the importance of preexisting tumor immune contexture. Previous findings highlight strong correlation between early peak levels of CAR-T cells after treatment initiation and treatment response. Maintaining an optimal CAR T-cell-to-tumor burden ratio is essential for sustained responses. Systemic and tumor immune contexture affects therapy outcomes, revealing preexisting immunity's role in CAR T-cell efficacy. The mechanistic impact of CAR-T cells was investigated using pre- and posttreatment biopsies, revealing specific markers associated with treatment response in refractory large B-cell lymphoma, across patients receiving CAR T-cell therapy in the second- and third-line settings, supporting precision medicine in developing next-generation cell therapies for hematologic malignancies. The evolution of the tumor microenvironment with therapy lines was also demonstrated, supporting earlier intervention with CAR T-cell therapy. Ongoing translational efforts, including single-cell omics analysis, aim to uncover additional factors that affect outcomes to develop more potent treatments.

Kaplan Meier estimates of progression-free survival in the pMMR population (optimized cut-point), according to IO status (a) and to both IO status and treatment arm (b).Legend: HR: hazard ratio, NR: not reached. Control arm indicates FOLFOXIRI plus bevacizumab. Atezo arm indicates FOLFOXIRI plus bevacizumab and atezolizumab.

Multiplex immunofluorescence and immunohistochemistry (mIF/IHC) are increasingly employed antibody-based technologies that use tissue sparingly and facilitate the detection of co-localized or neighboring biomarkers. Specifically, these platforms enable spatial analyses of the tumor microenvironment as well as extended applications, for example, describing normal tissue anatomy, autoimmunity, infectious diseases, etc. mIF/IHC has greatly enhanced biomarker discovery efforts, and a growing number of studies suggest superiority to traditional IHC. Standardization of staining approaches, reporting of image analysis strategies and resultant data is critical for facilitating cross-study comparisons, validation, deployment, and generalization of findings. To address this challenge, The Society for Immunotherapy of Cancer (SITC) previously published two articles providing best practice guidelines for mIF/IHC staining, image analysis, and data sharing. Here, SITC convened stakeholders to develop the third article in the series, a consensus checklist for scientific reporting of mIF/IHC data to support and complement the best practice guidelines. The checklist includes critical components of mIF/IHC applications to be defined within publications such as detailed descriptions of analytical validation; image acquisition, selection, and registration methods; and cell clustering and spatial analysis strategies, amongst others. Such information will help with data reproducibility and comparison across studies towards future drug and assay development.

Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, was approved for patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy (ZUMA-1, NCT02348216), as well as for those refractory to or relapsing within 12 months of first-line chemoimmunotherapy (ZUMA-7, NCT03391466). Recent molecular classifications of LBCL based on genetic factors shown to associate with response to R-CHOP and other chemo-immunotherapy based standard of care regimens have not been shown to associate with response to axi-cel in LBCL. Methods: To advance our understanding of the impact of tumor biology on response to axi-cel, we performed a detailed characterization of the tumor microenvironment (TME) using a multi-omic approach, integrating data from proteomics, transcriptomics and genomics offering a comprehensive view of biological systems, which we named Atlas. To construct the LBCL Atlas, we applied multiple technologies to 267 vendor-procured tumor samples from LBCL patients at diagnosis: (i) IHC panels, capturing spatial information at the protein and cellular level by counting and positioning cells of interest, (ii) Transcriptomics via RNA sequencing (RNA-seq) and Nanostring hybridization technology, (iii) Genomics, focusing on somatic mutation analysis through whole-exome sequencing (WES). Advanced mathematical and bioinformatics processing was employed to extract biological insights by combining both linear (multimodal factor analysis) and non-linear (self-organizing maps) methodologies. This effort resulted in a graphical representation of both complementary and overlapping signatures. Using samples with different prognostic outcomes and data from ZUMA-1 and ZUMA-7 axi-cel clinical trials, we further explored the evolution of the TME throughout disease progression and different lines of treatment. We focused on both adaptive immunity (lymphocytes, NK cells, etc.) and innate immunity (macrophages, MDSCs), examining the TME clusters defined by Atlas to characterize distinct tumor microenvironments. This Atlas provided an alternative to the cell-of-origin classification and other genetically based classifications of LBCL, based on TME. We will present evolutionary changes though lines of therapy to less favorable tumor microenvironments and, through the projection of clinical trial samples, demonstrate that the Atlas is a powerful tool for exploring mechanisms behind treatment response and disease progression. This includes the association of immune cell populations, such as T-cell and macrophage phenotypes and overall immune cell contexture within the TME, and other biomarkers with disease progression and treatment response. Michael D. Mattie, Regis Perbost, Aurelie Auguste, Alexia Papadopoulos, Jenny J. Kim, Ioana Kloos, Gayatri Tiwari, Justin Budka, Darawan Rinchai, Simone Filosto, Rhine Shen, Davide Bedognetti, Jérôme Galon. Multi-omic characterization of tumor microenvironment evolution in LBCL across treatment lines: Insights from Atlas classification and axicabtagene ciloleucel trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 867.

Kaplan Meier estimates of progression-free survival in the overall population (optimized cut-point), according to IO status (a) and to both IO status and treatment arm (b).Legend: HR: hazard ratio, NR: not reached. Control arm indicates FOLFOXIRI plus bevacizumab. Atezo arm indicates FOLFOXIRI plus bevacizumab and atezolizumab.

The phase 3 ZUMA-7 trial in second-line large B cell lymphoma demonstrated superiority of anti-CD19 CAR T cell therapy (axicabtagene ciloleucel (axi-cel)) over standard of care (SOC; salvage chemotherapy followed by hematopoietic transplantation) ( NCT03391466 ). Here, we present a prespecified exploratory analysis examining the association between pretreatment tumor characteristics and the efficacy of axi-cel versus SOC. B cell gene expression signature (GES) and CD19 expression associated significantly with improved event-free survival for axi-cel ( P = 0.0002 for B cell GES; P = 0.0165 for CD19 expression) but not SOC ( P = 0.9374 for B cell GES; P = 0.5526 for CD19 expression). Axi-cel showed superior event-free survival over SOC irrespective of B cell GES and CD19 expression ( P = 8.56 × 10 –9 for B cell GES high; P = 0.0019 for B cell GES low; P = 3.85 × 10 –9 for CD19 gene high; P = 0.0017 for CD19 gene low). Low CD19 expression in malignant cells correlated with a tumor GES consisting of immune-suppressive stromal and myeloid genes, highlighting the inter-relation between malignant cell features and immune contexture substantially impacting axi-cel outcomes. Tumor burden, lactate dehydrogenase and cell-of-origin impacted SOC more than axi-cel outcomes. T cell activation and B cell GES, which are associated with improved axi-cel outcome, decreased with increasing lines of therapy. These data highlight differences in resistance mechanisms to axi-cel and SOC and support earlier intervention with axi-cel.

Tertiary Lymphoid Structures (TLS) are lymphoid structures commonly associated with improved survival of cancer patients and response to immunotherapies. However, conflicting reports underscore the need to consider TLS heterogeneity and multiple features such as TLS size, composition, and maturation status, when assessing their functional impact. With the aim of gaining insights into TLS biology and evaluating the prognostic impact of TLS maturity in Non-Small Cell Lung Carcinoma (NSCLC), we developed a multiplex immunofluorescent (mIF) panel including T cell (CD3, CD8), B cell (CD20), Follicular Dendritic cell (FDC) (CD21, CD23) and mature dendritic cell (DC-LAMP) markers. We deployed this panel across a cohort of primary tumor resections from NSCLC patients (N=406) and established a mIF image analysis workstream to specifically detect TLS structures and evaluate the density of each cell phenotype. We assessed the prognostic significance of TLS size, number, and composition, to develop a TLS scoring system representative of TLS biology within a tumor. TLS relative area, (total TLS area divided by the total tumor area), was the most prognostic TLS feature (C-index: 0.54, p = 0.04). CD21 positivity was a marker driving the favorable prognostic impact, where CD21+ CD23- B cells (C-index: 0.57, p = 0.04) and CD21+ CD23- FDC (C-index: 0.58, p = 0.01) were the only prognostic cell phenotypes in TLS. Combining the three most robust prognostic TLS features: TLS relative area, the density of B cells, and FDC CD21+ CD23- we generated a TLS scoring system that demonstrated strong prognostic value in NSCLC when considering the effect of age, sex, histology, and smoking status. This TLS Score also demonstrated significant association with Immunoscore, EGFR mutational status and gene expression-based B-cell and TLS signature scores. It was not correlated with PD-L1 status in tumor cells or immune cells. In conclusion, we generated a prognostic TLS Score representative of the TLS heterogeneity and maturity undergoing within NSCLC tissues. This score could be used as a tool to explore how TLS presence and maturity impact the organization of the tumor microenvironment and support the discovery of spatial biomarker surrogates of TLS maturity, that could be used in the clinic.

In clinical practice, the administration of adjuvant chemotherapy (ACT) following tumor surgical resection raises a critical dilemma for stage II colon cancer (CC) patients. The prognostic features used to identify high-risk CC patients rely on the pathological assessment of tumor cells. Currently, these factors are considered for stratifying patients who may benefit from ACT at early CC stages. However, the extent to which these factors predict clinical outcomes (i.e. recurrence, survival) remains highly controversial, also uncertainty persists regarding patients' response to treatment, necessitating further investigation. Therefore, an imperious need is to explore novel biomarkers that can reliably stratify patients at risk, to optimize adjuvant treatment decisions. Recently, we evaluated the prognostic and predictive value of Immunoscore (IS), an immune digital-pathology assay, in stage II CC patients. IS emerged as the sole significant parameter for predicting disease-free survival (DFS) in high-risk patients. Moreover, IS effectively stratified patients who would benefit most from ACT based on their risk of recurrence, thus predicting their outcomes. Notably, our findings revealed that digital IS outperformed the visual quantitative assessment of the immune response conducted by expert pathologists. The latest edition of the WHO classification for digestive tumor has introduced the evaluation of the immune response, as assessed by IS, as desirable and essential diagnostic criterion. This supports the revision of current cancer guidelines and strongly recommends the implementation of IS into clinical practice as a patient stratification tool, to guide CC treatment decisions. This approach may provide appropriate personalized therapeutic decisions that could critically impact early-stage CC patient care.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We report 4-year results of the phase II randomized AtezoTRIBE study. Eligible patients with metastatic colorectal cancer (mCRC) received first-line fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/bevacizumab (control group, n = 73) or FOLFOXIRI/bevacizumab plus atezolizumab (experimental group, n = 145). We present overall survival (OS) and updated outcomes according to tumor immune-related biomarkers, both in the intention-to-treat (ITT) population and the cohort of patients with proficient mismatch repair (pMMR) tumors. Median follow-up was 45.2 months (IQR, 42.6-49.2). In the ITT population, median OS was 33.0 and 27.2 months for experimental and control groups, respectively (hazard ratio [HR], 0.78 [80% CI, 0.61 to 0.98]; P = .084). An interaction effect between Immunoscore Immune-Checkpoint (IC) and treatment arm was observed ( Pint, .089), with higher benefit from atezolizumab in the Immunoscore IC-high group. In the pMMR cohort (N = 202), median OS was 30.8 and 29.2 months for experimental and control groups, respectively (HR, 0.80 [80% CI, 0.63 to 1.02]; P = .117). Interactions between treatment group and tumor mutational burden (TMB) and Immunoscore IC were reported ( Pint, .043 and .092, respectively), with patients bearing TMB-high and Immunoscore IC-high tumors deriving higher benefit from the addition of atezolizumab. First-line FOLFOXIRI/bevacizumab plus atezolizumab improves OS in patients with mCRC. In the pMMR group, patients with Immunoscore IC-high and/or TMB-high tumors are identified as a subgroup of interest to further develop this treatment.