Phase I/II Evaluation of a Cancer Lysate Vaccine and Montanide(R) ISA-51 VG With Entinostat and Nivolumab as Adjuvant Therapy Following Chemoradiation Therapy With or Without Surgery for Locally Advanced Esophageal Cancer

* INCLUSION CRITERIA:
* Participants with clinical Stage II (T2/N0-N1; T3/N0) or Stage III (T1-T2/N2, T3/N1-N2) EsC per 8th edition TNM Staging System who have histologically documented or suspected residual disease in the esophagus or regional nodes following nCRT. Diagnosis must be confirmed by the NIH Laboratory of Pathology.
* No prior anti-PD1/anti-PD-L1 therapy for their EsC.
* Participant must be enrolled within 16 weeks following completion of nCRT or nCRT/surgery
* ECOG performance status of 0-1.
* 18 years of age or older
* Participant must be willing to co-enroll on 06C0014 (Prospective Analysis of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies) allowing for the use of tumor or normal tissues for correlative experiments pertaining to this protocol and related translational research efforts in the Thoracic Surgery Branch (TSB).
* Adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters (all eligibility assessment/enrollment bloodwork must be done at NIH no more than 2 weeks prior to initiation of study therapy):

  * Absolute neutrophil count greater than 1500/mm\^3
  * Platelet count greater than 100,000/mm\^3
  * Hemoglobin greater than 8 g/dL (participants may receive transfusions to meet this parameter)
  * INR \<= 1.5 x ULN
  * Total bilirubin \<1.5 x upper limits of normal (except those with Gilberts disease)
  * Serum creatinine less than or equal to 1.6 mg/mL or the eGFR (calculated per institutional standards) must be greater than 60 mL/min/1.73m\^2
* Oxygen saturation equal to or greater than 92% on room air within 2 weeks of initiation of study therapy.
* Seronegative for HIV antibody by bloodwork performed at NIH no more than 4 weeks prior to initiation of study therapy.
* Seronegative for active hepatitis B, and seronegative for hepatitis C antibody by bloodwork performed at NIH no more than 4 weeks prior to initiation of study therapy. If hepatitis C antibody test is positive, then participant must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
* Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) within 28 days prior to initiation of study therapy, for the duration of study participation and up to 5 months after the last dose of study therapy.
* Participants who are breastfeeding or plan to breastfeed must agree to discontinue/postpone breastfeeding while receiving investigational treatment and for 5 months after the last dose study therapy.
* Participants must be able to understand and willing to sign an informed consent.

EXCLUSION CRITERIA:

* Participants who are receiving any other investigational agents
* Participants with a history of pneumonitis will be excluded unless cleared by Pulmonary Medicine consultants
* Participants requiring chronic systemic treatment with steroids above physiologic doses.
* Participants receiving warfarin anticoagulation, who cannot be transitioned to other agents such as enoxaparin or dabigatran, and for whom anticoagulants cannot be held for up to 24 hours.
* Participants with uncontrolled hypertension (\>160/95) at screening, unstable coronary disease evidenced by EKG evidence of cardiac ischemia or uncontrolled arrhythmias, unstable angina, decompensated CHF (\>NYHA Class II), or myocardial infarction within 6 months prior to initiation of study therapy.
* Participants with any of the following pulmonary function abnormalities: FEV, \< 35% predicted; DLCO \< 35% predicted (post-bronchodilator); based on assessment performed no more than 4 weeks prior to initiation of study therapy.
* Participant pregnancy.
* Other malignancy requiring treatment with the exception of localized skin cancer amenable to topical therapies
* Uncontrolled intercurrent illness occurring within 3 months prior to initiation of study therapy that would limit compliance with study requirements. Intercurrent illness may include any conditions uncovered during screening assessments (physical examination, laboratory assessments, etc.) that, in the judgment of the investigator, precludes participation because it could present disproportionate risk to the participant