Elizabeth Franzmann

Emerging evidence suggests that not only the frequency and composition of tumor-infiltrating leukocytes but also their spatial organization might be a major determinant of tumor progression and response to therapy. Therefore, mapping and analyzing the fine tumor immune architecture could potentially provide insights for predicting cancer prognosis. Here, we performed an explorative, prospective clinical study to assess whether structures within the tumor microenvironment can predict recurrence after salvage surgery in head and neck squamous cell carcinoma (HNSCC). The major immune subsets were measured using flow cytometry and co-detection by indexing (CODEX) multiparametric imaging. Flow cytometry underestimated the number of PMN-MDSCs and neutrophils in the tumor and overestimated the tumor-infiltrating lymphocyte frequency. An ad hoc computational framework was used to identify and analyze discrete cellular neighborhoods. A high frequency of tertiary lymphoid structures composed of CD31highCD38high plasma cells was associated with reduced recurrence after surgery in HNSCC. These data support the notion that the structural architecture of the tumor immune microenvironment plays an essential role in tumor progression and indicates that type 1 tertiary lymphoid structures and long-lived CD31highCD38high plasma cells are associated with good prognosis in HNSCC.Significance:Imaging the spatial tumor immune microenvironment and evaluating the presence of type 1 tertiary lymphoid structures enables prediction of recurrence after surgery in patients with head and neck squamous cell carcinoma.

Emerging evidence suggests that not only the frequency and composition of tumor-infiltrating leukocytes but also their spatial organization might be a major determinant of tumor progression and response to therapy. Therefore, mapping and analyzing the fine tumor immune architecture could potentially provide insights for predicting cancer prognosis. Here, we performed an explorative, prospective clinical study to assess whether structures within the tumor microenvironment can predict recurrence after salvage surgery in head and neck squamous cell carcinoma (HNSCC). The major immune subsets were measured using flow cytometry and co-detection by indexing (CODEX) multiparametric imaging. Flow cytometry underestimated the number of PMN-MDSCs and neutrophils in the tumor and overestimated the tumor-infiltrating lymphocyte frequency. An ad hoc computational framework was used to identify and analyze discrete cellular neighborhoods. A high frequency of tertiary lymphoid structures composed of CD31highCD38high plasma cells was associated with reduced recurrence after surgery in HNSCC. These data support the notion that the structural architecture of the tumor immune microenvironment plays an essential role in tumor progression and indicates that type 1 tertiary lymphoid structures and long-lived CD31highCD38high plasma cells are associated with good prognosis in HNSCC.Significance:Imaging the spatial tumor immune microenvironment and evaluating the presence of type 1 tertiary lymphoid structures enables prediction of recurrence after surgery in patients with head and neck squamous cell carcinoma.

Emerging evidence suggests that not only the frequency and composition of tumor-infiltrating leukocytes but also their spatial organization might be a major determinant of tumor progression and response to therapy. Therefore, mapping and analyzing the fine tumor immune architecture could potentially provide insights for predicting cancer prognosis. Here, we performed an explorative, prospective clinical study to assess whether structures within the tumor microenvironment can predict recurrence after salvage surgery in head and neck squamous cell carcinoma (HNSCC). The major immune subsets were measured using flow cytometry and co-detection by indexing (CODEX) multiparametric imaging. Flow cytometry underestimated the number of PMN-MDSCs and neutrophils in the tumor and overestimated the tumor-infiltrating lymphocyte frequency. An ad hoc computational framework was used to identify and analyze discrete cellular neighborhoods. A high frequency of tertiary lymphoid structures composed of CD31highCD38high plasma cells was associated with reduced recurrence after surgery in HNSCC. These data support the notion that the structural architecture of the tumor immune microenvironment plays an essential role in tumor progression and indicates that type 1 tertiary lymphoid structures and long-lived CD31highCD38high plasma cells are associated with good prognosis in HNSCC.Significance: Imaging the spatial tumor immune microenvironment and evaluating the presence of type 1 tertiary lymphoid structures enables prediction of recurrence after surgery in patients with head and neck squamous cell carcinoma.

Objective: To examine the expression of candidate markers for micrometastasis. Study Design: Cross-sectional analysis of subjects with oral cavity carcinomas who underwent sentinel lymph node biopsy (SLNB) and subsequent immunohistochemical (IHC) analysis. Subjects and Methods: Two groups were identified based on SLNB status: negative SLNB (19/30) and positive SLNB (11/30). Specimens underwent IHC using conjugated monoclonal antibodies for membrane type-1 matrix metalloproteinase (MT1-MMP), CD44, focal adhesion kinase-1, and E-cadherin. Staining results were evaluated to determine if a particular marker was associated with SLNB status or other histopathologic prognosticators. Results: For MT1-MMP, 21 percent (3/14) of evaluable specimens stained positively in the SLNB(−) group and 67 percent (4/6) stained positively in the SLNB(+) group (P = 0.12). No statistically significant association was seen between any marker's staining pattern and SLNB status alone. When MT1-MMP staining was evaluated in tumors with SLNB(+) or perineural invasion (PNI) present on histopathology, six of nine specimens (67%) stained positively for MT1-MMP, vs one of 11 (9%) in specimens lacking either negative prognosticator (P = 0.016, RR = 7.33). Conclusion: Preliminary results suggest that MT1-MMP positivity in primary tumor specimens may identify aggressive tumor types, evidenced by the presence of micrometastasis or PNI.