Persistence and enrichment of dominant T cell clonotypes in expanded tumor-infiltrating lymphocytes of breast cancer.

BACKGROUND: Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown promising results in cancer treatment, including breast cancer. However, clonal dynamics and clinical significance of TIL expansion ex vivo remain poorly understood. METHODS: We investigated T cell receptor (TCR) repertoire changes in expanded TILs from 19 patients with breast cancer. We compared TCR repertoire of TILs at different stages of expansion, including initial (2W TILs) and rapid expansion (REP TILs), and their overlap with formalin fixed paraffin embedded (FFPE) and peripheral blood. Additionally, we examined differences in TCR repertoire between CD4+ and CD8+ REP TILs. RESULTS: In descending order of proportion, average of 60% of the top 10% clonotypes of FFPE was retained in 2W TIL (60% in TRB, 64.7% in TRA). Among the overlapped clonotypes between 2W TILs and REP TILs, 69.9% was placed in top 30% of 2W TIL. The proportion of clonotypes in 2W TIL and REP TIL showed a significant positive correlation. CD4+ and CD8+ T cells show similar results in diversity and CDR3 length. CONCLUSIONS: Our study traces the changes in TILs repertoire from FFPE to 2W TIL and REP TIL and confirmed that clonotypes with high frequencies in TILs have a high likelihood of maintaining their priority throughout culture process.

Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy.

BACKGROUND: Adoptive transfer of in vitro expanded tumor-infiltrating lymphocytes (TILs) has been effective in regressing several types of malignant tumors. This study assessed the yield and factors influencing the successful expansion of tumor-infiltrating lymphocytes (TILs) from head and neck squamous cell carcinoma (HNSCC), along with their immune phenotypes. METHODS: TILs were expanded from 47 surgically resected HNSCC specimens and their metastasized lymph nodes. The cancer tissues were cut into small pieces (1-2 mm) and underwent initial expansion for 2 weeks. Tumor location, smoking history, stromal TIL percentage, human papillomavirus infection, and programmed death-ligand 1 score were examined for their impact on successful expansion of TILs. Expanded TILs were evaluated by flow cytometry using fluorescence-activated cell sorting. A second round of TIL expansion following the rapid expansion protocol was performed on a subset of samples with successful TIL expansion. RESULTS: TILs were successfully expanded from 36.2% samples. Failure was due to contamination (27.6%) or insufficient expansion (36.2%). Only the stromal TIL percentage was significantly associated with successful TIL expansion (p = 0.032). The stromal TIL percentage also displayed a correlation with the expanded TILs per fragment (r = 0.341, p = 0.048). On flow cytometry analysis using 13 samples with successful TIL expansion, CD4 + T cell dominancy was seen in 69.2% of cases. Effector memory T cells were the major phenotype of expanded CD4 + and CD8 + T cells in all cases. CONCLUSION: We could expand TILs from approximately one-third of HNSCC samples. TIL expansion could be applicable in HNSCC samples with diverse clinicopathological characteristics.

Association of Dietary Total Antioxidant Capacity with Cancer Recurrence and Mortality among Breast Cancer Survivors: A Prospective Cohort Study.

Antioxidants decrease the risk of breast cancer by reducing oxidative stress, but the association between dietary total antioxidant capacity (DTAC) and cancer recurrence has not yet been investigated. The present study aimed to test the hypothesis that DTAC is inversely associated with cancer recurrence and mortality in breast cancer patients. Breast cancer patients (n = 603) who underwent breast cancer surgery and a dietary survey within 5 years after surgery were recruited. This study observed disease-free survival (DFS) and mortality in breast cancer patients according to DTAC calculated based on 24-hr dietary recall. Total DTAC was significantly lower in patients with cancer recurrence than in those without. DFS was positively associated with the total DTAC (p = 0.005) and DTAC of vegetables and legumes (p = 0.001 and p = 0.010), respectively. However, total DTAC was not associated with mortality. Cox proportional hazards regression analysis showed that total DTAC (HR: 0.44, 95% CI 0.26-0.94) and DTAC of vegetables (HR: 0.30, 95% CI 0.14-0.65) and legumes (HR: 0.38, 95% CI 0.18-0.73) were inversely associated with cancer recurrence after adjusting for confounding factors. This study was the first to indicate that total DTAC and DTAC of vegetables and legumes could be beneficial in decreasing breast cancer recurrence.

Assessment of Pain Onset and Maximum Bearable Pain Thresholds in Physical Contact Situations.

With the development of robot technology, robot utilization is expanding in industrial fields and everyday life. To employ robots in various fields wherein humans and robots share the same space, human safety must be guaranteed in the event of a human-robot collision. Therefore, criteria and limitations of safety need to be defined and well clarified. In this study, we induced mechanical pain in humans through quasi-static contact by an algometric device (at 29 parts of the human body). A manual apparatus was developed to induce and monitor a force and pressure. Forty healthy men participated voluntarily in the study. Physical quantities were classified based on pain onset and maximum bearable pain. The overall results derived from the trials pertained to the subjective concept of pain, which led to considerable inter-individual variation in the onset and threshold of pain. Based on the results, a quasi-static contact pain evaluation method was established, and biomechanical safety limitations on forces and pressures were formulated. The pain threshold attributed to quasi-static contact can serve as a safety standard for the robots employed.

CCR10-mediated Enhancement of T Cell Trafficking for Improved Tumor Immunotherapy.

BACKGROUND/AIM: The effectiveness of adoptive T cell therapy for solid tumors remains suboptimal, partly attributed to insufficient T cell infiltration into the tumor site. A promising strategy involves directing T cells towards the tumor utilizing tumor-specific chemokine receptors. MATERIALS AND METHODS: We analyzed chemokine receptor expression in activated T cells and chemokine expression in breast and lung cancer using The Cancer Genome Atlas (TCGA) data. Subsequently, we generated 1G4 T cell receptor-engineered T (TCR-T) cells with CCR10 and performed in vitro and in vivo efficacy tests. RESULTS: CCR10 exhibited insufficient expression in various human T cells. Analysis of TCGA RNA sequencing data revealed elevated expression of the chemokine CCL28, the corresponding chemokine for CCR10, in breast and lung cancer. Consequently, we generated CCR10-1G4 TCR-T cells. CCR10-1G4 dual expressing TCR-T cells exhibited comparable cellular cytotoxicity but increased mobility compared to 1G4 TCR-T cells in vitro. Furthermore, injecting CCR10-1G4 dual expressing TCR-T cells into a xenograft tumor model demonstrated enhanced in vivo trafficking and a greater reduction of tumor burden. CONCLUSION: This study highlights the potential of CCR10 for developing efficient adoptive T-cell treatments targeting solid tumors.

Assessment of pressure pain thresholds in collisions with collaborative robots.

In recent years, safety issues surrounding robots have increased in importance, as more robots are in close contact with humans, both in industrial fields and elsewhere. Safety standards for industrial robots operating in specific spaces have been established, but no such standards have been specified for collaborative and service robots. To establish safety standards for such robots, we assessed pressure pain thresholds for collisions between humans and robots, under the assumption that the pain threshold is lower than the mild injury threshold. The pressure pain threshold for collision with a robot was measured in 90 male Korean adults using a homemade collision system. The pain thresholds were measured three times at 15 sites, including the forehead. The highest threshold was 196.1 ± 85.8 N/cm2 at the back of the hand, and the lowest was 65.1 ± 22.6 N/cm2 at an arm nerve. Moderate thresholds, i.e., 100-120 N/cm2, were noted on the forehead, neck muscle, ball of the thumb, and shin. The thresholds of participants < 30 years of age were lower, by 3-33%, than those of participants aged > 30 years. Thresholds differed by body mass index only at certain sites, including the shoulder joint, neck, and back of the hand. The pressure pain threshold depended on individual characteristics, body site, and age. The threshold relevant to potential human-robot collisions was determined to be between 65.1 ± 22.6 and 196.1 ± 85.8 N/cm2.