<p>GBM, the most common primary malignant brain tumor in adults, has an overall dismal prognosis. Immunotherapy targeting the PD-1/PD-L1 axis has shown limited success in GBM. Resistance to therapies involves different pathways like autophagy. Detecting LC3B expression provides a simple technique for monitoring autophagy. Our goal was to understand the interplay between PD-L1 and LC3B in GBM prognosis and treatment strategies.&#xa0;The study analyzed 61 GBM specimens to assess the immunohistochemical expression of PD-L1 and LC3B with investigating their correlation with various clinicopathological parameters with assessing the impact of PD-L1 and LC3B expression on patients’ survival and the relation between both markers.&#xa0;Both PD-L1 and LC3B were significantly associated with clinicopathological parameters, including Karnofsky performance score (KPS)(<i>P</i> = 0.028 and 0.004 respectively), surgical resection extent (<i>P</i> = 0.023 and 0.002), treatment response(<i>P</i> = 0.015, <i>P</i> ≤ 0.001), patient outcome(<i>p</i> ≤ 0.001), and recurrence (<i>P</i> ≤ 0.001). There was a statistically significant inverse correlation between overall survival (OS) and both PD-L1 and LC3B expression. Additionally, there was a statistically significant inverse correlation between progression-free survival (PFS) and LC3B expression. PD-L1 expression, extent of resection and adjuvant chemotherapy were identified as independent prognostic factors for overall survival in GBM cases. A statistically significant positive relation existed between PD-L1 and LC3B (<i>P</i> ≤ 0.001).&#xa0;Results of this study suggest that the robust expression of PD-L1 in glioblastoma is associated with poor prognosis. Additionally, high expression of LC3B in GBM suggests increased autophagic activity which associated with unfavourable outcome. Combining immunotherapy with autophagy modulators could be a promising approach for improving GBM treatment.</p>