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Updated: Jan 21, 2026
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Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
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The Folate Pathway Inhibitor Pemetrexed Pleiotropically Enhances Effects of Cancer Immunotherapy
David A Schaer1, Sandaruwan Geeganage2, Nelusha Amaladas1
1Lilly Research Laboratories, Eli Lilly and Company, New York, New York.
Summary
Pemetrexed enhances anti-cancer immune responses by inducing immunogenic cell death and boosting T-cell function. Combining pemetrexed with PD-1 blockade further amplifies these effects for improved cancer treatment.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Chemotherapy and immunotherapy combinations show promise for cancer treatment.
- Pemetrexed/carboplatin with anti-PD-1 is approved for non-small cell lung cancer, but mechanisms are unclear.
Purpose of the Study:
- To elucidate the mechanistic rationale behind the efficacy of pemetrexed/anti-PD-L1 combination therapy.
- To investigate the effects of pemetrexed on immunogenic cell death (ICD) and T-cell function.
Main Methods:
- Utilized mouse tumor models (MC38, Colon26) and high-content biomarker studies.
- Assessed ICD using calreticulin and HMGB-1 immunoassays.
- Evaluated T-cell metabolic function via Seahorse analysis.
Main Results:
- Pemetrexed alone increased T-cell activation, induced ICD in tumor cells, and enhanced T-cell mitochondrial function.
- Combination of pemetrexed with anti-PD-L1 resulted in increased antitumor efficacy and immune activation.
Conclusions:
- Pemetrexed augments anti-cancer immunity via tumor-intrinsic ICD and T-cell-intrinsic mechanisms.
- Combining pemetrexed with PD-1 blockade significantly enhances intratumor immune responses and T-cell activity.
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