Development and Performance of a CD8 Gene Signature for Characterizing Inflammation in the Tumor Microenvironment across Multiple Tumor Types

Abstract

Across multiple tumor types, immune checkpoint inhibitors (ICIs) have demonstrated clinical benefit to patients with cancer, yet there is a need to identify predictive biomarkers of response to these therapies. A multiparameter gene expression profiling–based tumor inflammation assay may offer robust characterization of the tumor microenvironment, thereby extending the utility of single-gene analysis or immunohistochemistry (IHC) in predicting response to ICIs. The authors interrogated 1778 commercially procured, formalin-fixed, paraffin-embedded samples using gene expression profiling and pathology-assisted digital CD8 IHC. A machine-learning approach was used to develop gene expression signatures that predicted CD8+ immune cell abundance as surrogates for tumor inflammation in melanoma and squamous cell carcinoma of the head and neck samples. An assay for a 16-gene CD8 signature was developed and analytically validated across 12 tumor types. CD8 signature scores correlated with CD8 IHC in a platform-independent manner, and inflammation prevalence was similar between assay methods for all tumor types except prostate cancer and small cell lung cancer. In retrospective analyses, CD8 signature scores were associated with progression-free survival and overall survival with nivolumab in patients with urothelial carcinoma from CheckMate 275. This study demonstrated that the CD8 signature assay can be used to accurately quantify CD8+ immune cell abundance in the tumor microenvironment and has potential clinical utility for determining patients with cancer likely to respond to ICIs. Across multiple tumor types, immune checkpoint inhibitors (ICIs) have demonstrated clinical benefit to patients with cancer, yet there is a need to identify predictive biomarkers of response to these therapies. A multiparameter gene expression profiling–based tumor inflammation assay may offer robust characterization of the tumor microenvironment, thereby extending the utility of single-gene analysis or immunohistochemistry (IHC) in predicting response to ICIs. The authors interrogated 1778 commercially procured, formalin-fixed, paraffin-embedded samples using gene expression profiling and pathology-assisted digital CD8 IHC. A machine-learning approach was used to develop gene expression signatures that predicted CD8+ immune cell abundance as surrogates for tumor inflammation in melanoma and squamous cell carcinoma of the head and neck samples. An assay for a 16-gene CD8 signature was developed and analytically validated across 12 tumor types. CD8 signature scores correlated with CD8 IHC in a platform-independent manner, and inflammation prevalence was similar between assay methods for all tumor types except prostate cancer and small cell lung cancer. In retrospective analyses, CD8 signature scores were associated with progression-free survival and overall survival with nivolumab in patients with urothelial carcinoma from CheckMate 275. This study demonstrated that the CD8 signature assay can be used to accurately quantify CD8+ immune cell abundance in the tumor microenvironment and has potential clinical utility for determining patients with cancer likely to respond to ICIs. Immune checkpoint inhibitors (ICIs) targeting the programmed death-1/programmed death ligand 1 (PD-1/PD-L1) axis have demonstrated significant clinical benefit across a range of tumor types.1Büttner R. Longshore J.W. Lopez-Rios F. Merkelbach-Bruse S. Normanno N. Rouleau E. Penault-Llorca F. Implementing TMB measurement in clinical practice: considerations on assay requirements.ESMO Open. 2019; 4: e000442Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar There is, however, a critical need to identify subsets of patients who are likely to respond to ICIs or alternative therapies.2Chan T.A. Yarchoan M. Jaffee E. Swanton C. Quezada S.A. Stenzinger A. Peters S. Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic.Ann Oncol. 2019; 30: 44-56Abstract Full Text Full Text PDF PubMed Scopus (692) Google Scholar Precision medicine is an emerging approach for guiding treatment for patients with cancer, considering the molecular and genomic variability between tumors.3Malone M. profiling for cancer PubMed Scopus Google Scholar and methods have developed to the tumor microenvironment to identify biomarkers for patients who are likely to respond to a biomarkers are and in to tumor that to of tumor and can to an to and R. R. M. A. E. M. C. A. N. A. A. genomic biomarkers for checkpoint PubMed Scopus Google M. M. E. A. A. S.A. A. clinical response to PubMed Scopus Google M. S. S. M. M. C. E. M. immunohistochemistry study in clinical of Oncol. Full Text Full Text PDF PubMed Scopus Google F. F. N. F. C. A. S. M. A. A. M. for treatment of PubMed Scopus Google A. A. M. F. N. N. S. in with PubMed Scopus Google N. A. S. R. S. R. F. N. T.A. and microenvironment immunotherapy with Full Text Full Text PDF PubMed Scopus Google A. N. F. C. R. C. T.A. to in cell lung PubMed Scopus Google C. The Full Text Full Text PDF PubMed Scopus Google Scholar A in the has associated with clinical in patients with E. Immune checkpoint and potential PubMed Scopus Google M. M. C. E. C. C. A. immune PubMed Scopus Google S. of and in the melanoma tumor microenvironment is Scopus Google Scholar and inflammation biomarkers are and in for with the clinical of ICIs across multiple tumor M. M. E. F. N. S. R. Peters S. E. nivolumab in or lung PubMed Scopus Google M. M. M. A. R. M. and of in patients with and clinical Oncol. 4: PubMed Scopus Google S. A. R. R. A. S. and in PubMed Scopus Google R. N. M. Longshore J.W. Lopez-Rios F. Penault-Llorca F. 1 immunohistochemistry a of and clinical in lung Oncol. PubMed Scopus Google Scholar CD8+ immune using immunohistochemistry can be used as a for inflammation that is associated with in a range of tumor of in the of the immune in PubMed Scopus Google T.A. E. or the of immune in PubMed Scopus Google C. CD8+ as a in lung a of lung PubMed Scopus Google Scholar on tumor immune or may be of a and clinical of ICIs in patients with has to the of a of IHC and for tumor J.W. of IHC and assay and across multiple PubMed Scopus Google Scholar In to biomarkers of tumor that with are as surrogates for potential immune using using and tumor burden have associated with clinical of ICIs across a of tumor A. A. M. F. N. N. S. in with PubMed Scopus Google N. A. S. R. S. R. F. N. T.A. and microenvironment immunotherapy with Full Text Full Text PDF PubMed Scopus Google Rouleau E. E. A. of in the of Full Text Full Text PDF PubMed Scopus Google E. A. A. R. burden and of nivolumab and in with in lung Full Text Full Text PDF PubMed Scopus Google A. C. E. S. M. F. in lung cancer with a tumor PubMed Scopus Google A. A. R. M. N. S.A. M. R. of in patients with from the Oncol. PubMed Scopus Google A. M. M. R. A. S. S.A. F. of burden with in patients with with analysis of the Oncol. Full Text Full Text PDF PubMed Scopus Google Scholar methods as IHC or have to multiple gene offer the potential to or of of with a R. Longshore J.W. Lopez-Rios F. Merkelbach-Bruse S. Normanno N. Rouleau E. Penault-Llorca F. Implementing TMB measurement in clinical practice: considerations on assay requirements.ESMO Open. 2019; 4: e000442Abstract Full Text Full Text PDF PubMed Scopus (131) Google M. M. E. A. A. S.A. A. clinical response to PubMed Scopus Google M. gene expression profiling from small and and clinical formalin-fixed, paraffin-embedded using the 2019; Full Text Full Text PDF PubMed Scopus Google Scholar gene are for profiling tumor for multiple genomic in and R. Longshore J.W. Lopez-Rios F. Merkelbach-Bruse S. Normanno N. Rouleau E. Penault-Llorca F. Implementing TMB measurement in clinical practice: considerations on assay requirements.ESMO Open. 2019; 4: e000442Abstract Full Text Full Text PDF PubMed Scopus (131) Google A. M. M. R. A. S. S.A. F. of burden with in patients with with analysis of the Oncol. Full Text Full Text PDF PubMed Scopus Google A. M. burden for TMB in clinical samples to immunotherapy treatment 2019; PubMed Scopus Google Scholar expression profiling have used to the of multiple tumor types and gene expression signatures of tumor R. R. M. A. E. M. C. A. N. A. A. genomic biomarkers for checkpoint PubMed Scopus Google M. M. E. A. A. S.A. A. clinical response to PubMed Scopus Google M. A. A. A. S. S. C. A. A. S. A. in urothelial carcinoma a Oncol. Full Text Full Text PDF PubMed Scopus Google A. M. A. A. A. C. N. and gene expression and to in urothelial PubMed Scopus Google S. A. expression of tumor PubMed Scopus Google Scholar as and have developed to of and treatment for patients with The of the PubMed Scopus Google C. S. S. N. M. of the and using paraffin-embedded tumor PubMed Scopus Google M. M. R. E. F. C. S. M. A clinical study of in cancer from the and Open. Full Text Full Text PDF PubMed Scopus Google Scholar signatures of inflammation in the have associated with response to ICIs in multiple tumor R. R. M. A. E. M. C. A. N. A. A. genomic biomarkers for checkpoint PubMed Scopus Google S. R. A. A. immune as the tumor inflammation signature from The PubMed Scopus Google Scholar have signatures that are associated with response to M. M. E. A. A. S.A. A. clinical response to PubMed Scopus Google M. A. A. A. S. S. C. A. A. S. A. in urothelial carcinoma a Oncol. Full Text Full Text PDF PubMed Scopus Google Scholar an signature was associated with response to treatment with nivolumab in of patients with urothelial carcinoma A. M. A. A. A. C. N. and gene expression and to in urothelial PubMed Scopus Google Scholar these that a targeting multiple in may offer robust characterization of the and extending the utility of gene expression that of multiple gene signatures can be used to of inflammation and immune in may have predictive for response to ICIs with of biomarkers as CD8 or the clinical utility of gene to of the an assay for a 16-gene signature was developed to be used as a of inflammation in the The CD8 signature was using from melanoma and squamous cell carcinoma of the head and neck and analytically validated across tumor types with CD8 IHC and of inflammation the of CD8 signature scores across scores using were with using between the CD8 signature and of tumor the of the CD8 signature and inflammation gene S. A. expression of tumor PubMed Scopus Google S. R. A. A. immune as the tumor inflammation signature from The PubMed Scopus Google Scholar in predicting CD8 expression on immune and expression on tumor IHC were In retrospective in samples from patients with from CheckMate were between the CD8 signature and the clinical of and of the CD8 to were from commercially procured, formalin-fixed, paraffin-embedded samples of tumor types and of tumor were of and is in clinical of the CD8 samples were from patients with and tumor expression who were with nivolumab as of the study CheckMate M. A. A. A. S. S. C. A. A. S. A. in urothelial carcinoma a Oncol. Full Text Full Text PDF PubMed Scopus Google Scholar for the analysis was CD8 IHC was pathology-assisted digital using a CD8 an was used and was using all tumor types, the and were and was with were using an to using and were using and CD8 IHC scores were as the of CD8+ immune of in the tumor tumor and tumor between CD8 signature scores and CD8 CD8 IHC scores were to expression was on tumor using the IHC assay in with an to the and was a of expression on of tumor is in to on all tumor tumor and were A of was a on and to tumor and of the tumor the and as a a similar of was on an to be used for the of was and samples were using a gene signatures were using and alternative and Immune was and from from commercially samples using the was using the in were to the and S. of using analysis of or PubMed Scopus Google a PubMed Scopus Google Scholar using in with A. F. C. S. M. PubMed Scopus Google Scholar was used for abundance for from with or a PubMed Scopus Google Scholar and were using The of of was with the in a for expression analysis of digital gene expression PubMed Scopus Google Scholar and to The CD8 signature was developed and analytically validated using the S. R. M. N. of an gene signature with CD8 expression immunohistochemistry (IHC) in multiple tumor Oncol. 2019; Google Scholar This to tumor of and expression of all on the were using an with A of from an was for using the from was used in were in and for to was to a of 1 and samples were for with was to a of a were to the and the was using an with was to and were using a to and molecular samples were using and using a were using a with were using were and to and were to was were on in the with for of of samples in the assay and samples with expression variability the of was The of on the were was in of samples from tumor to of to The expression of gene was as of was using and with were with an were significant The tumor inflammation signature S. R. A. A. immune as the tumor inflammation signature from The PubMed Scopus Google Scholar and CD8+ abundance S. A. expression of tumor PubMed Scopus Google Scholar were developed using the gene expression M. M. E. A. A. S.A. A. clinical response to PubMed Scopus Google S. A. expression of tumor PubMed Scopus Google Scholar In was on the of as for using the targeting from the were as of was and were to using were to was on the of as for using the Immune targeting to digital gene expression were using with the of was using the and were to A machine-learning a to develop a with on the as the and CD8 IHC as the The of that the with CD8 IHC using and samples was for samples The and with for and was to to a 16-gene expression for predicting CD8 IHC. The CD8 signature from the and was validated across tumor types using from a of samples that This from patients with cancer cancer carcinoma cell lung cancer cancer cancer prostate cancer cell carcinoma small cell lung cancer and as as the and used to develop the CD8 signature for the CD8 and signature were from the gene expression of of the in gene in the CD8 signature was a and the was as the of gene expression and signature scores were as M. M. E. A. A. S.A. A. clinical response to PubMed Scopus Google S. A. expression of tumor PubMed Scopus Google Scholar using analysis of from the and was scores for are in were with for and were using for Google Scholar between CD8 signature scores and CD8 the for of CD8 IHC was from the multiple using and samples. The was of samples were between CD8 IHC and gene expression signature scores were for tumor inflammation prevalence and a was developed to inflammation prevalence CD8 signature and CD8 IHC scores were on a were as or or a to the CD8 signature inflammation or was the to the CD8 IHC between and gene expression signature scores were using the and across and were using the to CD8 signature scores from across samples from of the 12 tumor types were using a was in samples of the across samples from of the 12 tumor samples were across and CD8 signature scores for were used to a that the between the CD8 signature and the of and were used to between CD8 signature scores and survival from CheckMate survival and overall survival on retrospective of patients with CD8 signature scores in the to or CD8 signature scores expression on of tumor and of The of of the on the was using of samples from of 12 tumor types to from to were from Across all the from was for of the to cell gene a significant was an of 1778 CD8+ immune cell abundance was and IHC in using samples from a of 12 tumor types. for or in gene A machine-learning approach was used to gene expression signatures that correlated with CD8+ immune cell abundance in the IHC in and samples and on these analyses, a 16-gene CD8 signature was and to CD8 IHC was in tumor types. The range of CD8 CD8 IHC and the CD8 signature was across of the tumor types lung cancer, and cancer samples CD8 scores and IHC and A CD8 scores was in tumor types with CD8 expression IHC cancer, and CD8 signature scores correlated with CD8 IHC scores across multiple tumor types in CD8 IHC associated with CD8 signature were for all tumor types except cancer and were CD8 signature scores were Across all 12 tumor types of CD8 signature scores the from the Across the used for assay and samples of scores the that the CD8 signature accurately predicted CD8 IHC across multiple tumor types. the samples in study were in of scores the from the the of CD8+ immune in the was across the 12 tumor types using CD8 IHC and the CD8 signature as for A was to the of inflammation prevalence that may across tumor types. the of samples with CD8 IHC scores or CD8 signature scores that from to Across multiple tumor types, prevalence was similar between assay methods and on the used to In and however, prevalence to the assay methods was the in the range of CD8 IHC and CD8 signature scores in these samples A study was to the and of the CD8 signature assay across and across samples from all tumor types was Across for from to for and from to were in across multiple tumor types assay CD8 signature scores were in across samples tumor that were of the range of inflammation in of the 12 tumor types were Across all tumor types, as a of CD8 signature and was to in samples with CD8 signature scores The of the CD8 signature was across using samples from a of patients with and between gene expression for the in the CD8 using of and for gene expression were across the to to and to for the Immune and with were across for with a range of expression across or were for or was CD8 signature using the expression of all in the correlated with using for all with the expression of in the CD8 signature of CD8 signature scores using and is for of CD8 signature scores using gene gene expression The of gene expression signatures to CD8+ immune cell in the was Across the and of the inflammation signatures correlated with CD8 IHC the CD8 correlated with tumor expression IHC with and signature scores in and samples expression on and of tumor Across all 12 tumor types, CD8 IHC CD8 signature scores correlated with expression on tumor the clinical utility of the CD8 signature in predicting in the and clinical response to the CD8 signature was in samples from patients with the samples from patients in CheckMate were for CD8 were for the CD8 signature and were for CD8 IHC and the CD8 for tumor for or were similar between all patients and the was for all patients and in the was for all patients and for the In the and a between CD8 signature and CD8 IHC that was with clinical samples was similar to that in commercially samples In retrospective analyses, with survival were patients CD8 signature as to or was for patients with CD8 signature scores in the for patients with CD8 signature scores in the and for patients with scores in the and was in patients with CD8 signature scores in the with patients with CD8 signature scores in the and for patients with scores in the and of CD8 signature scores with and were for clinical as expression on tumor and of of inflammation in the have to be predictive for the clinical of E. Immune checkpoint and potential PubMed Scopus Google M. M. C. E. C. C. A. immune PubMed Scopus Google S. of and in the melanoma tumor microenvironment is Scopus Google Scholar The of IHC is analysis using a assay the of multiple biomarkers in the and may a robust characterization of R. R. M. A. E. M. C. A. N. A. A. genomic biomarkers for checkpoint PubMed Scopus Google F. F. N. F. C. A. S. M. A. A. M. for treatment of PubMed Scopus Google S. A. expression of tumor PubMed Scopus Google M. A. from in cell carcinoma Oncol. 2019; Google Scholar a gene study the of an assay for a 16-gene expression of and to be used as a of inflammation in tumor samples. of CD8+ immune can be used as a robust of inflammation for tumor types, is associated with response to of in the of the immune in PubMed Scopus Google T.A. E. or the of immune in PubMed Scopus Google A. M. A. A. A. C. N. and gene expression and to in urothelial PubMed Scopus Google Scholar The CD8 signature was developed to CD8+ immune cell abundance across multiple tumor types. of with for the CD8 signature or is likely to be associated with immune cell abundance S. A. expression of tumor PubMed Scopus Google Scholar expression of with may immune cell and can to S. R. A. A. immune as the tumor inflammation signature from The PubMed Scopus Google Scholar for a of S. R. A. A. immune as the tumor inflammation signature from The PubMed Scopus Google S. R. N. M. S. M. M. cancer PubMed Scopus Google Scholar of the to the CD8 signature and is the gene in the with expression that was associated with scores or with clinical benefit with M. M. E. A. A. S.A. A. clinical response to PubMed Scopus Google S. R. A. A. immune as the tumor inflammation signature from The PubMed Scopus Google Scholar across samples that inflammation the CD8 signature correlated with that CD8 IHC in all tumor types except cancer and that gene signature may be as an of inflammation across a range of tumor types. tumor types, prevalence of was similar for and that a CD8 signature assay has the potential to be in a clinical to CD8+ immune cell abundance was in tumor types, with M. and clinical of and in small cell lung cancer 2019; PubMed Scopus Google Scholar and a between CD8 signature and CD8 IHC scores was a in CD8 signature scores in samples the for CD8 signature CD8 IHC for tumor types and in variability in the of inflammation are to the need for for determining of inflammation in tumor types with of CD8+ immune cell abundance in the patients with have between abundance and clinical benefit with yet the clinical of CD8+ immune cell is for patients with tumor N. S. M. The tumor immune of prostate 2019; PubMed Scopus Google A. A. A. immune and treatment of patients with prostate PubMed Scopus Google Scholar The of CD8 IHC and CD8 signature scores were in samples for tumor types, and the between CD8 IHC and CD8 signature was with the prevalence of inflammation in of samples. to the of assay for profiling patients with tumor types as and to CD8 is an of response to in tumor types the prevalence of CD8+ immune cell is A critical need to identify biomarkers of response to ICIs has to the and of a of and in to treatment for patients with M. C. biomarkers for immune checkpoint and for 2019; PubMed Scopus Google Scholar of that are or the and is and of or and have that molecular assay are to variability in and and that of can be R. Longshore J.W. Lopez-Rios F. Merkelbach-Bruse S. Normanno N. Rouleau E. Penault-Llorca F. Implementing TMB measurement in clinical practice: considerations on assay requirements.ESMO Open. 2019; 4: e000442Abstract Full Text Full Text PDF PubMed Scopus (131) Google A. M. burden for TMB in clinical samples to immunotherapy treatment 2019; PubMed Scopus Google Scholar of in for clinical on and as as to and R. Longshore J.W. Lopez-Rios F. Merkelbach-Bruse S. Normanno N. Rouleau E. Penault-Llorca F. Implementing TMB measurement in clinical practice: considerations on assay requirements.ESMO Open. 2019; 4: e000442Abstract Full Text Full Text PDF PubMed Scopus (131) Google A. M. burden for TMB in clinical samples to immunotherapy treatment 2019; PubMed Scopus Google C. Peters S. N. and for clinical 2019; Full Text Full Text PDF PubMed Scopus Google and for of an in with a Scholar a for analysis of M. Quezada S.A. Swanton C. of tumor PubMed Scopus Google C. F. M. of the of in PubMed Scopus Google Scholar the of gene expression to with and to significant to M. S. of and on the and of Full Text Full Text PDF PubMed Scopus Google N. E. of and of lung tumor on expression Full Text Full Text PDF PubMed Scopus Google Scholar the and in assay have of CD8+ immune cell abundance in the The assay may have potential utility for inflammation in The CD8 signature assay demonstrated using the to CD8 signature scores across 12 tumor types. was with and in clinical for determining biomarkers in patients with and and of and Scholar the that of on the demonstrated is that the to gene expression with multiple and is for of gene was demonstrated for samples with CD8 signature scores CD8 signature scores correlated with CD8 IHC scores on all platform-independent for the CD8 signature as a of CD8+ immune cell were for alternative tumor inflammation the robust of inflammation gene expression signatures and potential of multiple for a of are as assay and be an for a clinical C. Peters S. N. and for clinical 2019; Full Text Full Text PDF PubMed Scopus Google S.A. clinical and PubMed Scopus Google Scholar The assay with in an This can from small of samples as of a to of the with alternative and assay M. gene expression profiling from small and and clinical formalin-fixed, paraffin-embedded using the 2019; Full Text Full Text PDF PubMed Scopus Google Scholar may be to the utility of the assay for from or samples. are to the clinical utility of the CD8 signature as a assay for inflammation in the of inflammation in the have to be predictive for the clinical of R. R. M. A. E. M. C. A. N. A. A. genomic biomarkers for checkpoint PubMed Scopus Google E. Immune checkpoint and potential PubMed Scopus Google M. M. C. E. C. C. A. immune PubMed Scopus Google S. of and in the melanoma tumor microenvironment is Scopus Google Scholar of patients with from CheckMate clinical with nivolumab in patients with CD8+ immune cell or with expression on of tumor using A. M. A. A. A. C. N. and gene expression and to in urothelial PubMed Scopus Google Scholar An gene expression was associated with response to M. A. A. A. S. S. C. A. A. S. A. in urothelial carcinoma a Oncol. Full Text Full Text PDF PubMed Scopus Google Scholar In analysis of patients from CheckMate that the CD8 signature correlated with CD8 IHC and that CD8 signature scores were associated with and with of these with and predictive is S. R. S. A. N. of a signature gene expression profiling in patients with urothelial carcinoma from CheckMate 2019; Google Scholar with and in tumor types are to for patients as CD8 signature and to the CD8 signature is or predictive of response to nivolumab or ICIs. Across all tumor types CD8 signature scores with expression on tumor a for CD8 signature was in are to the between CD8 signature scores and expression on tumor immune or The of between potential biomarkers of response to ICIs that or all of these may of inflammation in the and a for to the potential of multiple biomarkers in R. R. M. A. E. M. C. A. N. A. A. genomic biomarkers for checkpoint PubMed Scopus Google M. M. E. F. N. S. R. Peters S. E. nivolumab in or lung PubMed Scopus Google M. A. S. M. and immunotherapy in 2019; Scholar retrospective analysis of from CheckMate in response and for patients with a of CD8 IHC and signature A. M. A. A. A. C. N. and gene expression and to in urothelial PubMed Scopus Google Scholar across multiple tumor types have demonstrated response and with ICIs in patients with TMB with with patients with scores for of these R. R. M. A. E. M. C. A. N. A. A. genomic biomarkers for checkpoint PubMed Scopus Google Scholar that gene expression signatures may methods of and may to medicine for patients with R. R. M. A. E. M. C. A. N. A. A. genomic biomarkers for checkpoint PubMed Scopus Google A. M. A. A. A. C. N. and gene expression and to in urothelial PubMed Scopus Google M. C. biomarkers for immune checkpoint and for 2019; PubMed Scopus Google S. C. of for predicting response to checkpoint a and Oncol. 2019; PubMed Scopus Google Scholar This study demonstrated that an analytically validated gene expression assay for the 16-gene CD8 signature can identify an in the and may identify patients that are from potential to CD8 signature on In of patients with the CD8 signature was associated with the clinical of is to the predictive of the CD8 signature in patients likely to respond to ICIs and to the clinical utility of gene expression signatures to medicine in patients with cancer.

Topics & Concepts