Dataset Information

Association between Tumor Mutational Burden, Stromal CD8⁺ Tumor-Infiltrating Lymphocytes, and Clinical Factors in Cervical Cancers Treated with Radiotherapy.

ABSTRACT:

Background

Tumor mutational burden (TMB) and stromal CD8-positive tumor-infiltrating lymphocytes (CD8⁺TILs) serve important roles in antitumor immune responses to radiotherapy. This study aimed to elucidate the association between TMB, CD8⁺TILs, and clinical factors in patients with cervical cancer treated with radiotherapy.

Methods

Patients with squamous cell carcinoma of the uterine cervix treated with definitive radiotherapy, and with available somatic mutation data and immunohistochemical staining data from identical tumor tissues, were enrolled retrospectively. The association between TMB and/or CD8⁺TIL density and patient characteristics, mutation profiles, and treatment outcome was analyzed.

Results

The study analyzed 44 patients (median follow-up period, 61 months). There was no significant correlation between TMB and CD8⁺TIL density, or between TMB or CD8⁺TIL density and patient characteristics. TMB-high or CD8⁺TIL density-low status was associated with worse overall survival and distant metastasis-free survival; the predictive value of these factors became greater when used in combination. TMB-high or CD8⁺TIL density-high status was associated with ARID1A mutations.

Conclusions

These data indicate independence of TMB and CD8⁺TIL density and the involvement of ARID1A alterations in antitumor immune responses in patients with cervical cancers treated with radiotherapy, warranting further mechanistic research and prospective validation.

SUBMITTER: Ruan H

PROVIDER: S-EPMC9954714 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Association between Tumor Mutational Burden, Stromal CD8<sup>+</sup> Tumor-Infiltrating Lymphocytes, and Clinical Factors in Cervical Cancers Treated with Radiotherapy.

Ruan Hanguang H Oike Takahiro T Sato Hiro H Ando Ken K Ohno Tatsuya T

Cancers 20230214 4

<h4>Background</h4>Tumor mutational burden (TMB) and stromal CD8-positive tumor-infiltrating lymphocytes (CD8<sup>+</sup>TILs) serve important roles in antitumor immune responses to radiotherapy. This study aimed to elucidate the association between TMB, CD8<sup>+</sup>TILs, and clinical factors in patients with cervical cancer treated with radiotherapy.<h4>Methods</h4>Patients with squamous cell carcinoma of the uterine cervix treated with definitive radiotherapy, and with available somatic mut ...[more]

PMID: 36831552

Similar Datasets

Project description:BACKGROUND:Immuno-oncology and cancer immunotherapies are areas of intense research. The numbers and locations of CD8+ tumor-infiltrating lymphocytes (TILs) are important measures of the immune response to cancer with prognostic, pharmacodynamic, and predictive potential. We describe the development, validation, and application of advanced image analysis methods to characterize multiple immunohistochemistry-derived CD8 parameters in clinical and nonclinical tumor tissues. METHODS:Commercial resection tumors from nine cancer types, and paired screening/on-drug biopsies of non-small-cell lung carcinoma (NSCLC) patients enrolled in a phase 1/2 clinical trial investigating the PD-L1 antibody therapy durvalumab (NCT01693562), were immunostained for CD8. Additional NCT01693562 samples were immunostained with a CD8/PD-L1 dual immunohistochemistry assay. Whole-slide scanning was performed, tumor regions were annotated by a pathologist, and images were analyzed with customized algorithms using Definiens Developer XD software. Validation of image analysis data used cell-by-cell comparison to pathologist scoring across a range of CD8+ TIL densities of all nine cancers, relying primarily on 95% confidence in having at least moderate agreement regarding Lin concordance correlation coefficient (CCC = 0.88-0.99, CCC_lower = 0.65-0.96). RESULTS:We found substantial variability in CD8+ TILs between individual patients and across the nine types of human cancer. Diffuse large B-cell lymphoma had several-fold more CD8+ TILs than some other cancers. TIL densities were significantly higher in the invasive margin versus tumor center for carcinomas of head and neck, kidney and pancreas, and NSCLC; the reverse was true only for prostate cancer. In paired patient biopsies, there were significantly increased CD8+ TILs 6 weeks after onset of durvalumab therapy (mean of 365 cells/mm2 over baseline; P = 0.009), consistent with immune activation. Image analysis accurately enumerated CD8+ TILs in PD-L1+ regions of lung tumors using the dual assay and also measured elongate CD8+ lymphocytes which constituted a fraction of overall TILs. CONCLUSIONS:Validated image analysis accurately enumerates CD8+ TILs, permitting comparisons of CD8 parameters among tumor regions, individual patients, and cancer types. It also enables the more complex digital solutions needed to better understand cancer immunity, like analysis of multiplex immunohistochemistry and spatial evaluation of the various components comprising the tumor microenvironment. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT01693562 . Study code: CD-ON-MEDI4736-1108. Interventional study (ongoing but not currently recruiting). Actual study start date: August 29, 2012. Primary completion date: June 23, 2017 (final data collection date for primary outcome measure).

Dataset Information

Association between Tumor Mutational Burden, Stromal CD8⁺ Tumor-Infiltrating Lymphocytes, and Clinical Factors in Cervical Cancers Treated with Radiotherapy.

Background

Methods

Results

Conclusions

Publications

Association between Tumor Mutational Burden, Stromal CD8<sup>+</sup> Tumor-Infiltrating Lymphocytes, and Clinical Factors in Cervical Cancers Treated with Radiotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Association between Tumor Mutational Burden, Stromal CD8+ Tumor-Infiltrating Lymphocytes, and Clinical Factors in Cervical Cancers Treated with Radiotherapy.

Background

Methods

Results

Conclusions

Publications

Association between Tumor Mutational Burden, Stromal CD8<sup>+</sup> Tumor-Infiltrating Lymphocytes, and Clinical Factors in Cervical Cancers Treated with Radiotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Association between Tumor Mutational Burden, Stromal CD8⁺ Tumor-Infiltrating Lymphocytes, and Clinical Factors in Cervical Cancers Treated with Radiotherapy.