Possible Reason for the Failure of Immunotherapy in Glioblastoma
It is seen that the majority of both primary and recurrent tumors have a low density of TILs. While all the cases of tumors have CD3+ TILs. A significantly higher CD8+ TIL density was demonstrated by quantitative analysis of TILs at recurrence.
Moreover, between primary and recurrent groups, there was no difference observed in CD3+, CD4+ and PD-1+ TIL density. Treatment target like anti-PD-1 antibodies with immune checkpoint inhibition, blocks PD-1/PD-L1 interactions. This restores the effector T cell proliferation and function.
Immunotherapy in Glioblastoma
In a specific type of cancer – melanoma, it was seen that response to anti-PD-1 immunotherapy is associated with a higher density of CD8+ TILs. However, earlier clinical trials that have been conducted using anti-PD-1 immunotherapy in glioblastoma, demonstrated limited success.
Studies like the CheckMate 143 trial and similar ones demonstrated no significant overall survival benefit in recurrent glioblastoma with anti-PD-1 when compared to the anti-angiogenic drug bevacizumab.
However, another study (Cloughesy et a) states that anti-PD-1 therapy significantly increases the overall survival if given before and after recurrent tumor resection than only after recurrent surgery.
“The level of T cell infiltration seen in this small cohort of matched primary and recurrent glioblastoma tissue was low. Though the number of CD8+ TILs was significantly higher in recurrent compared to primary tumours, overall TIL density at recurrence was still mild. PD-1+ TILs in particular were absent in the majority of our cases. Whether this is why many clinical trials using anti-PD-1 immunotherapy have not shown significant survival benefit in glioblastoma requires further investigation,” say the Tooney Research Team.
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