Dataset Information

Tumor cell HLA class I expression and pathologic response following neoadjuvant immunotherapy for newly diagnosed head and neck cancer.

ABSTRACT:

Objectives

Biomarkers are needed to identify patients likely to respond to neoadjuvant immunotherapy (NIT) prior to receiving definitive treatment.

Materials and methods

We hypothesized that expression of tumor cell HLA class I would correlate with pathologic response (PR) following NIT for primary untreated head and neck cancer. Multispectral immunofluorescence of pre- and post-treatment biopsy specimens from a neoadjuvant study of bintrafusp alfa, a dual TGF-β and PD-L1 inhibitor, was performed.

Results

Discordant expression of tumor cell HLA class I and PD-L1 measured by multispectral immunofluorescence was observed with most positive tumor cells expressing HLA class I or PD-L1 but not both. Spatial analysis revealed colocalization between tumor parenchyma T cells and HLA class I positive tumors cells, but no clear colocalization between T cells and PD-L1 positive tumor cells. Greater pre-treatment tumor cell HLA class I expression, but not PD-L1 expression or tumor T cell infiltration, correlated with the development of a PR. Additionally, increased tumor cell HLA class I expression after NIT compared to before NIT correlated with development of a PR, whereas inconsistent changes in PD-L1 and T cell infiltration were observed after treatment in all patients.

Conclusions

These data provide the rationale for the study of tumor cell HLA class I expression in larger prospective studies powered to determine the performance of biomarkers of PR in newly diagnosed HNSCC patients receiving NIT.

SUBMITTER: Robbins Y

PROVIDER: S-EPMC9974754 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Tumor cell HLA class I expression and pathologic response following neoadjuvant immunotherapy for newly diagnosed head and neck cancer.

Robbins Yvette Y Friedman Jay J Redman Jason J Sievers Cem C Lassoued Wiem W Gulley James L JL Allen Clint T CT

Oral oncology 20230120

<h4>Objectives</h4>Biomarkers are needed to identify patients likely to respond to neoadjuvant immunotherapy (NIT) prior to receiving definitive treatment.<h4>Materials and methods</h4>We hypothesized that expression of tumor cell HLA class I would correlate with pathologic response (PR) following NIT for primary untreated head and neck cancer. Multispectral immunofluorescence of pre- and post-treatment biopsy specimens from a neoadjuvant study of bintrafusp alfa, a dual TGF-β and PD-L1 inhibito ...[more]

PMID: 36682187

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Project description:PurposeHead and neck lymphedema (HNL) following radiation therapy for head and neck cancer (HNC) causes patient morbidity. Predicting individual patients' risk of HNL after treatment is challenging. We aimed to identify the demographic, disease-related, and treatment-related factors associated with external and internal HNL following treatment of HNC with definitive or adjuvant radiation therapy.Methods and materialsRelevant clinical, pathologic, and dosimetric data for 76 consecutive patients who received definitive or adjuvant radiation ± chemotherapy were retrospectively collected from a single institution. Multivariable models predictive of external and internal lymphedema using clinicopathologic variables alone and in combination with dosimetric variables were constructed and optimized using competing risk regression.ResultsAfter median follow-up of 550 days, the incidence of external and internal HNL at 360 days was 70% and 34%, respectively. When evaluating clinical and treatment-related factors alone, number of lymph nodes removed and advanced adenopathy status were predictive of external lymphedema. With incorporation of dosimetric variables, the optimized model included the percentage volume of the contralateral lymph node level VII receiving 30Gy V30 ≥50%, number of lymph nodes removed, and advanced adenopathy status. For internal lymphedema, our clinicopathologic model identified both adjuvant radiation, as opposed to definitive radiation, and advanced adenopathy status. With inclusion of a dosimetric variable, the optimized model included larynx V45 ≥50% and advanced adenopathy.ConclusionsHNL following HNC treatment is common. For both external and internal lymphedema, nodal disease burden at diagnosis predicts increased risk. For external lymphedema, increasing extent of lymph node dissection prior to adjuvant therapy increases risk. The contralateral level VII lymph node region is also predictive of external lymphedema when radiation dose to V30 is ≥50%, meriting investigation. For internal lymphedema, we confirm that increasing radiation dose to the larynx is the most significant dosimetric predictor of mucosal edema when larynx V45 is ≥50%.

Dataset Information

Tumor cell HLA class I expression and pathologic response following neoadjuvant immunotherapy for newly diagnosed head and neck cancer.

Objectives

Materials and methods

Results

Conclusions

Publications

Tumor cell HLA class I expression and pathologic response following neoadjuvant immunotherapy for newly diagnosed head and neck cancer.

Similar Datasets

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