Sophia Hernandez

Survival after resection of pancreatic cancer is similar with neoadjuvant gemcitabine-nab-paclitaxel or mFOLFIRINOX but one size will not fit all in the future

Colorectal cancer and liver metastases are a leading cause of cancer-related mortality. Overexpression of the immunostimulatory cytokine TNFSF14/LIGHT associates with improved survival and correlates with increased tumor-infiltrating lymphocytes in patients and a clinically relevant model of colorectal liver metastases. We demonstrate that LIGHT monotherapy activates T cells, but also induces T cell exhaustion and the recruitment of immunosuppressive elements. As colorectal liver metastases exhibit high levels of CTLA-4 expression, we combined LIGHT overexpression with anti-CTLA-4, leading to complete tumor control. The combination functions by homing tumor-infiltrating lymphocytes, inducing tumor antigen-specific T cells, and reversing T cell exhaustion. Whereas both LIGHT overexpression and anti-CTLA-4 increase tumor-promoting macrophages, the combination eliminates this population. The ability of LIGHT overexpression combined with CTLA-4 inhibition to reverse T cell exhaustion and myeloid cell suppression is supported by analysis of complementary patient cohorts and has strong clinical relevance, especially given that liver metastases contribute to immunotherapy resistance across various cancer types.

(1) Background: Comprehensive evaluation of guideline-concordant care (GCC) across all PDAC stages has yet to be thoroughly conducted. This study aimed to characterize treatment patterns and assess factors associated with receiving GCC among patients with pancreatic ductal adenocarcinoma (PDAC) in California. (2) Methods: Data on adult patients with PDAC were extracted from the California Cancer Registry (2004–2020). GCC is defined according to the recommendations provided by the National Comprehensive Cancer Network. We used multivariable logistic regression to identify factors associated with receiving GCC. A Cox model was used to examine the association of GCC with overall survival. (3) Results: A total of 50,346 PDAC patients were included (stage 1: 10%; stage 2: 25%; stage 3: 11%; stage 4: 54%). Only 46.7% of all patients received GCC (stage 1: 20%; stage 2: 40%; stage 3: 69%; stage 4: 50%). Only 31% of stage 1 patients underwent surgery. Factors inversely associated with receiving GCC were Hispanic ethnicity (OR 0.78; p < 0.001), Black race (OR 0.74; p < 0.001), having no insurance (OR 0.40; p < 0.001]), and a Charlson–Deyo score of ≥2 (OR 0.68; p < 0.001). Adherence to GCC was associated with improved survival (Hazard Ratio 0.39; p < 0.001). Notably, patients with stage 1 PDAC who received GCC had a median survival of 47 months vs. 8 months for those who did not. (4) Conclusions: Although stage 1 PDAC patients have the greatest potential for survival with GCC, only 20% of patients received such treatment. Thus, it is crucial to identify and address the modifiable factors contributing to these suboptimal care patterns.