RE:RE:RE:RE:RE:RE:CD8+ TiLs and T-cell exhaustionCD8+ TiL cells are critical mediators of cytotoxic effector function in cancer, however, in cancer, CD8+ TiL cells undergo a progressive loss of cytokine production and cytotoxicity, a state termed T-cell exhaustion as well as T-cell dysfuntion, resulting in a failure of T-cells to eradicate tumor cells in the tumor microenvironment (TME).
Also, high levels of PD-1 expression contribute to the characteristic dysfunction seen in exhausted CD8+ TiL cells. Correspondingly, in human tumors, a higher proportion of progenitor exhausted cells was associated with a greater likelihood of response to checkpoint blockade. While PD-1 blockade therapies have been successful in multiple tumor types, their effectiveness has been limited to between 10-20% of the patients treated.
Results from ONCY's AWARE-1 study showed that pelareorep treatment upregulated tumor PD-L1 expression, induced the generation and expansion of T cell clones, promoted tumor infiltration of CD8+ TiL cells, and increased the CelTIL score, a measure of tumor cellularity and inflammation associated with favorable clinical outcomes. Besides being able to overcome an immunosuppressive TME, pelareorp is a critical 'facilitator' in 'priming' the adaptive immune system in advance of PD-1 blockade, thus turning a 'cold' tumor into a 'hot' tumor that is more much conducive for PD-1 blockade, and a more effective I/O therapy than either agent alone.
https://www.newswire.ca/news-releases/oncolytics-biotech-r-and-solti-achieve-primary-endpoint-in-aware-1-study-871181269.html
March 24, 2024 -
Tumor-Infiltrating Lymphocytes (TILs) in Breast Cancer: Prognostic and Predictive Significance across Molecular Subtypes
" Tumor-infiltrating lymphocytes (TILs) are pivotal in the immune response against breast cancer (BC), with their prognostic and predictive significance varying across BC subtypes. In triple-negative BC (TNBC), higher TIL levels correlate with improved prognosis and treatment response, guiding therapeutic strategies and potentially offering avenues for treatment de-escalation. In metastatic TNBC, TILs identify patients with enhanced immunotherapy response. HER2+ BC, similar to TNBC, exhibits positive correlations between TILs and treatment response, especially in neoadjuvant settings."
" ... TILs hold considerable prognostic and predictive value in BC, with variations observed across different BC phenotypes. The most compelling evidence supporting the clinical significance of TILs is found in TNBC. Understanding the intricate relationship between TILs infiltration and prognosis in specific BC subtypes is crucial for the development of effective treatment strategies. Moreover, TILs have the potential to serve as predictive biomarkers, possibly guiding treatment decisions and optimizing patient outcomes."
https://www.mdpi.com/2227-9059/12/4/763