The tendency is that having an active immune system implied that patients survive longer. However, I have read in literature that the prognostic role of the immune system can be different accordingly to the the region from where the solid tumor had originally originated from. For example in mesothelioma the higher expression of tumor-infiltrating lymphocytes (TILs) is predictive of a better outcome for the patients. Likewise for triple negative breast cancer there are many examples in literature showing that the presence of TILs is an important predictor of pCT to neoadjuvant chemotherapy, or increased disease-free survival and OS in randomized adjuvant studies. However in hormone receptor (HR) positive and human epidermal receptor 2 (HER2) negative breast cancer high TILs correlated with worse outcomes. On the other hand, accordingly to retrospective studies on large clinical trials it has been demonstrated that high levels of TILs in the tumor is correlated with higher ki67 (a known marker for proliferation), worse time-to-progression and shorter survivals after recurrences had occurred.
What you think could explain such differences?
The problem is the definition of what constitute immune activatoin at the tumor site. AND TIL does not always mean active/functional lymphocytes at the tumor site. This is why the success of biologics is dependent on what the immune cell status/marker expression at the site. And TIL is only one part of WBCs. The role of neutrophils are now being seen as having impact on lymphocyte activation. Monocyte/macrophages also matter.
Thank you for your intriguing answer. Do yoi think that the neutrophils-to lymphocyte ratio a better predictor of the inactivation of the immune system rather than TILS and T-Regs?
It depends (it's probably tumor specific, site specific, and patient specific) . And I can only give you one example of where neutrophils might play a role. For the anti-PD-L1/PD-1 therapies, there are several biomarkers that have been proposed, 1) expression of PD-L1/PD-1 at the tumor site, 2) expression of PD-L1 on macrophages, 3) the level of PD-L1/PD-1 expression...
Recently, some have noticed that presence of neutrophils at the tumor site is a predictor of therapy success...meaning that the more neutrophil infiltration there is, the less likely the anti-PD-L1/PD-1 will work. Why? There is some evidence to suggest that the neutrophils may act as a barrier between the tumor and the T cells, so if the T cells can't get to the tumor cells, there is no point in using anti-PD-L1/PD-1.
As for T regs... I think they still play a role, but how much and where and how, depends.
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