High intratumoral CD8+ T‐cell infiltration is associated with improved survival in prostate cancer patients undergoing radical prostatectomy
Background A high density of CD8+ tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in prostate cancer remains controversial. The aim of our study was to evaluate the prognostic value of CD8+ TILs in prostate cancer patients under...
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| Vydané v: | The Prostate Ročník 81; číslo 1; s. 20 - 28 |
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| Hlavní autori: | , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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United States
Wiley Subscription Services, Inc
01.01.2021
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| ISSN: | 0270-4137, 1097-0045, 1097-0045 |
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| Abstract | Background
A high density of CD8+ tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in prostate cancer remains controversial. The aim of our study was to evaluate the prognostic value of CD8+ TILs in prostate cancer patients undergoing radical prostatectomy (RP). We hypothesized that elevated density of CD8+ TILs in the RP specimen would correlate with improved clinical outcomes. This information may be helpful for future immunotherapy clinical trial design and treatment selection.
Methods
Tumor microarrays constructed from 230 patients with localized prostate cancers who underwent RP from 2006 to 2012 at Roswell Park Comprehensive Cancer Center were analyzed retrospectively using immunohistochemistry. CD8+ cell density was evaluated using a computerized scoring system. The cohorts were separated by CD8+ TIL density at the 25th percentile (i.e., low <quartile 1 and high ≥quartile 1). The quartile 1 threshold was chosen through a “minimal p value approach” based on overall survival with correction of significance to adjust for multiple testing. Clinical outcomes were compared in the high versus low CD8+ TIL density groups.
Results
One hundred and forty‐nine (65%) patients had high risk diseases (Gleason >7 or pT3/4). The median follow‐up time was 8.4 years. High CD8+ TIL density was associated with improved 5‐year overall survival (98% vs. 91%, p = .01) and prostate cancer‐specific survival (99% vs. 95%, p = .04) compared with patients with low CD8+ TIL density. There was a trend toward higher 5‐year biochemical recurrence‐free survival and metastasis‐free survival in the cohort of patients with high CD8+ TIL density (52% vs. 38% and 86% vs. 73%, respectively), although the difference did not reach statistical significance (p = .18 and p = .05, respectively). In a multivariate analysis high CD8+ TIL density was an independent favorable prognostic factor for overall survival (hazards ratio = 0.38; 95% confidence interval: 0.17–0.87; p = .02). In contrast to the prognostic value of CD8+ TIL density, the CD8+ cell density in the matched normal prostate tissue was not associated with any clinical outcomes.
Conclusion
Intratumoral CD8+ T‐cell infiltration in the RP specimen is independently associated with improved survival after RP in this high‐risk prostate cancer cohort. Pre‐RP immunomodulation that promotes intratumoral CD8+ cytotoxic T‐cell infiltration may be beneficial for this population. |
|---|---|
| AbstractList | A high density of CD8
tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in prostate cancer remains controversial. The aim of our study was to evaluate the prognostic value of CD8
TILs in prostate cancer patients undergoing radical prostatectomy (RP). We hypothesized that elevated density of CD8
TILs in the RP specimen would correlate with improved clinical outcomes. This information may be helpful for future immunotherapy clinical trial design and treatment selection.
Tumor microarrays constructed from 230 patients with localized prostate cancers who underwent RP from 2006 to 2012 at Roswell Park Comprehensive Cancer Center were analyzed retrospectively using immunohistochemistry. CD8
cell density was evaluated using a computerized scoring system. The cohorts were separated by CD8
TIL density at the 25th percentile (i.e., low <quartile 1 and high ≥quartile 1). The quartile 1 threshold was chosen through a "minimal p value approach" based on overall survival with correction of significance to adjust for multiple testing. Clinical outcomes were compared in the high versus low CD8
TIL density groups.
One hundred and forty-nine (65%) patients had high risk diseases (Gleason >7 or pT3/4). The median follow-up time was 8.4 years. High CD8
TIL density was associated with improved 5-year overall survival (98% vs. 91%, p = .01) and prostate cancer-specific survival (99% vs. 95%, p = .04) compared with patients with low CD8
TIL density. There was a trend toward higher 5-year biochemical recurrence-free survival and metastasis-free survival in the cohort of patients with high CD8
TIL density (52% vs. 38% and 86% vs. 73%, respectively), although the difference did not reach statistical significance (p = .18 and p = .05, respectively). In a multivariate analysis high CD8
TIL density was an independent favorable prognostic factor for overall survival (hazards ratio = 0.38; 95% confidence interval: 0.17-0.87; p = .02). In contrast to the prognostic value of CD8
TIL density, the CD8
cell density in the matched normal prostate tissue was not associated with any clinical outcomes.
Intratumoral CD8
T-cell infiltration in the RP specimen is independently associated with improved survival after RP in this high-risk prostate cancer cohort. Pre-RP immunomodulation that promotes intratumoral CD8
cytotoxic T-cell infiltration may be beneficial for this population. A high density of CD8+ tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in prostate cancer remains controversial. The aim of our study was to evaluate the prognostic value of CD8+ TILs in prostate cancer patients undergoing radical prostatectomy (RP). We hypothesized that elevated density of CD8+ TILs in the RP specimen would correlate with improved clinical outcomes. This information may be helpful for future immunotherapy clinical trial design and treatment selection.BACKGROUNDA high density of CD8+ tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in prostate cancer remains controversial. The aim of our study was to evaluate the prognostic value of CD8+ TILs in prostate cancer patients undergoing radical prostatectomy (RP). We hypothesized that elevated density of CD8+ TILs in the RP specimen would correlate with improved clinical outcomes. This information may be helpful for future immunotherapy clinical trial design and treatment selection.Tumor microarrays constructed from 230 patients with localized prostate cancers who underwent RP from 2006 to 2012 at Roswell Park Comprehensive Cancer Center were analyzed retrospectively using immunohistochemistry. CD8+ cell density was evaluated using a computerized scoring system. The cohorts were separated by CD8+ TIL density at the 25th percentile (i.e., low <quartile 1 and high ≥quartile 1). The quartile 1 threshold was chosen through a "minimal p value approach" based on overall survival with correction of significance to adjust for multiple testing. Clinical outcomes were compared in the high versus low CD8+ TIL density groups.METHODSTumor microarrays constructed from 230 patients with localized prostate cancers who underwent RP from 2006 to 2012 at Roswell Park Comprehensive Cancer Center were analyzed retrospectively using immunohistochemistry. CD8+ cell density was evaluated using a computerized scoring system. The cohorts were separated by CD8+ TIL density at the 25th percentile (i.e., low <quartile 1 and high ≥quartile 1). The quartile 1 threshold was chosen through a "minimal p value approach" based on overall survival with correction of significance to adjust for multiple testing. Clinical outcomes were compared in the high versus low CD8+ TIL density groups.One hundred and forty-nine (65%) patients had high risk diseases (Gleason >7 or pT3/4). The median follow-up time was 8.4 years. High CD8+ TIL density was associated with improved 5-year overall survival (98% vs. 91%, p = .01) and prostate cancer-specific survival (99% vs. 95%, p = .04) compared with patients with low CD8+ TIL density. There was a trend toward higher 5-year biochemical recurrence-free survival and metastasis-free survival in the cohort of patients with high CD8+ TIL density (52% vs. 38% and 86% vs. 73%, respectively), although the difference did not reach statistical significance (p = .18 and p = .05, respectively). In a multivariate analysis high CD8+ TIL density was an independent favorable prognostic factor for overall survival (hazards ratio = 0.38; 95% confidence interval: 0.17-0.87; p = .02). In contrast to the prognostic value of CD8+ TIL density, the CD8+ cell density in the matched normal prostate tissue was not associated with any clinical outcomes.RESULTSOne hundred and forty-nine (65%) patients had high risk diseases (Gleason >7 or pT3/4). The median follow-up time was 8.4 years. High CD8+ TIL density was associated with improved 5-year overall survival (98% vs. 91%, p = .01) and prostate cancer-specific survival (99% vs. 95%, p = .04) compared with patients with low CD8+ TIL density. There was a trend toward higher 5-year biochemical recurrence-free survival and metastasis-free survival in the cohort of patients with high CD8+ TIL density (52% vs. 38% and 86% vs. 73%, respectively), although the difference did not reach statistical significance (p = .18 and p = .05, respectively). In a multivariate analysis high CD8+ TIL density was an independent favorable prognostic factor for overall survival (hazards ratio = 0.38; 95% confidence interval: 0.17-0.87; p = .02). In contrast to the prognostic value of CD8+ TIL density, the CD8+ cell density in the matched normal prostate tissue was not associated with any clinical outcomes.Intratumoral CD8+ T-cell infiltration in the RP specimen is independently associated with improved survival after RP in this high-risk prostate cancer cohort. Pre-RP immunomodulation that promotes intratumoral CD8+ cytotoxic T-cell infiltration may be beneficial for this population.CONCLUSIONIntratumoral CD8+ T-cell infiltration in the RP specimen is independently associated with improved survival after RP in this high-risk prostate cancer cohort. Pre-RP immunomodulation that promotes intratumoral CD8+ cytotoxic T-cell infiltration may be beneficial for this population. BackgroundA high density of CD8+ tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in prostate cancer remains controversial. The aim of our study was to evaluate the prognostic value of CD8+ TILs in prostate cancer patients undergoing radical prostatectomy (RP). We hypothesized that elevated density of CD8+ TILs in the RP specimen would correlate with improved clinical outcomes. This information may be helpful for future immunotherapy clinical trial design and treatment selection.MethodsTumor microarrays constructed from 230 patients with localized prostate cancers who underwent RP from 2006 to 2012 at Roswell Park Comprehensive Cancer Center were analyzed retrospectively using immunohistochemistry. CD8+ cell density was evaluated using a computerized scoring system. The cohorts were separated by CD8+ TIL density at the 25th percentile (i.e., low <quartile 1 and high ≥quartile 1). The quartile 1 threshold was chosen through a “minimal p value approach” based on overall survival with correction of significance to adjust for multiple testing. Clinical outcomes were compared in the high versus low CD8+ TIL density groups.ResultsOne hundred and forty‐nine (65%) patients had high risk diseases (Gleason >7 or pT3/4). The median follow‐up time was 8.4 years. High CD8+ TIL density was associated with improved 5‐year overall survival (98% vs. 91%, p = .01) and prostate cancer‐specific survival (99% vs. 95%, p = .04) compared with patients with low CD8+ TIL density. There was a trend toward higher 5‐year biochemical recurrence‐free survival and metastasis‐free survival in the cohort of patients with high CD8+ TIL density (52% vs. 38% and 86% vs. 73%, respectively), although the difference did not reach statistical significance (p = .18 and p = .05, respectively). In a multivariate analysis high CD8+ TIL density was an independent favorable prognostic factor for overall survival (hazards ratio = 0.38; 95% confidence interval: 0.17–0.87; p = .02). In contrast to the prognostic value of CD8+ TIL density, the CD8+ cell density in the matched normal prostate tissue was not associated with any clinical outcomes.ConclusionIntratumoral CD8+ T‐cell infiltration in the RP specimen is independently associated with improved survival after RP in this high‐risk prostate cancer cohort. Pre‐RP immunomodulation that promotes intratumoral CD8+ cytotoxic T‐cell infiltration may be beneficial for this population. Background A high density of CD8+ tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in prostate cancer remains controversial. The aim of our study was to evaluate the prognostic value of CD8+ TILs in prostate cancer patients undergoing radical prostatectomy (RP). We hypothesized that elevated density of CD8+ TILs in the RP specimen would correlate with improved clinical outcomes. This information may be helpful for future immunotherapy clinical trial design and treatment selection. Methods Tumor microarrays constructed from 230 patients with localized prostate cancers who underwent RP from 2006 to 2012 at Roswell Park Comprehensive Cancer Center were analyzed retrospectively using immunohistochemistry. CD8+ cell density was evaluated using a computerized scoring system. The cohorts were separated by CD8+ TIL density at the 25th percentile (i.e., low <quartile 1 and high ≥quartile 1). The quartile 1 threshold was chosen through a “minimal p value approach” based on overall survival with correction of significance to adjust for multiple testing. Clinical outcomes were compared in the high versus low CD8+ TIL density groups. Results One hundred and forty‐nine (65%) patients had high risk diseases (Gleason >7 or pT3/4). The median follow‐up time was 8.4 years. High CD8+ TIL density was associated with improved 5‐year overall survival (98% vs. 91%, p = .01) and prostate cancer‐specific survival (99% vs. 95%, p = .04) compared with patients with low CD8+ TIL density. There was a trend toward higher 5‐year biochemical recurrence‐free survival and metastasis‐free survival in the cohort of patients with high CD8+ TIL density (52% vs. 38% and 86% vs. 73%, respectively), although the difference did not reach statistical significance (p = .18 and p = .05, respectively). In a multivariate analysis high CD8+ TIL density was an independent favorable prognostic factor for overall survival (hazards ratio = 0.38; 95% confidence interval: 0.17–0.87; p = .02). In contrast to the prognostic value of CD8+ TIL density, the CD8+ cell density in the matched normal prostate tissue was not associated with any clinical outcomes. Conclusion Intratumoral CD8+ T‐cell infiltration in the RP specimen is independently associated with improved survival after RP in this high‐risk prostate cancer cohort. Pre‐RP immunomodulation that promotes intratumoral CD8+ cytotoxic T‐cell infiltration may be beneficial for this population. |
| Author | Xu, Bo Mohler, James L. Kalinski, Pawel Attwood, Kristopher Chatta, Gurkamal Guru, Khurshid Bshara, Wiam Yang, Yuanquan |
| AuthorAffiliation | 4. Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 1. Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 2. Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 3. Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 5. Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY |
| AuthorAffiliation_xml | – name: 4. Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY – name: 1. Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY – name: 2. Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH – name: 5. Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY – name: 3. Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY |
| Author_xml | – sequence: 1 givenname: Yuanquan orcidid: 0000-0002-5209-9247 surname: Yang fullname: Yang, Yuanquan organization: The Ohio State University Comprehensive Cancer Center – sequence: 2 givenname: Kristopher surname: Attwood fullname: Attwood, Kristopher organization: Roswell Park Comprehensive Cancer Center – sequence: 3 givenname: Wiam surname: Bshara fullname: Bshara, Wiam organization: Roswell Park Comprehensive Cancer Center – sequence: 4 givenname: James L. orcidid: 0000-0002-7726-3795 surname: Mohler fullname: Mohler, James L. organization: Roswell Park Comprehensive Cancer Center – sequence: 5 givenname: Khurshid surname: Guru fullname: Guru, Khurshid organization: Roswell Park Comprehensive Cancer Center – sequence: 6 givenname: Bo surname: Xu fullname: Xu, Bo organization: Roswell Park Comprehensive Cancer Center – sequence: 7 givenname: Pawel surname: Kalinski fullname: Kalinski, Pawel email: Pawel.Kalinski@RoswellPark.org organization: Roswell Park Comprehensive Cancer Center – sequence: 8 givenname: Gurkamal surname: Chatta fullname: Chatta, Gurkamal email: Gurkamal.Chatta@RoswellPark.org organization: Roswell Park Comprehensive Cancer Center |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33085799$$D View this record in MEDLINE/PubMed |
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A high density of CD8+ tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in... A high density of CD8 tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in prostate... BackgroundA high density of CD8+ tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in... A high density of CD8+ tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in prostate... |
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| SubjectTerms | Adult Aged Cancer surgery CD8 antigen CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - pathology Cell density Clinical outcomes Cohort Studies Cytotoxicity Humans Immunohistochemistry Immunomodulation Immunotherapy Infiltration Lymphocytes Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - pathology Male Metastases Middle Aged Multivariate Analysis Neoplasm Staging Patients Prognosis Prostate cancer Prostatectomy Prostatic Neoplasms - immunology Prostatic Neoplasms - mortality Prostatic Neoplasms - surgery radical prostatectomy Retrospective Studies Survival Rate tumor infiltrating lymphocyte tumor tissue microarray Urological surgery |
| Title | High intratumoral CD8+ T‐cell infiltration is associated with improved survival in prostate cancer patients undergoing radical prostatectomy |
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